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Special Issue "MicroRNA Regulation"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: closed (31 March 2016)

Special Issue Editor

Guest Editor
Prof. Dr. Y-h. Taguchi

Department of Physics, Chuo University, Tokyo, Japan
Website | E-Mail
Phone: +81 3 3817 1791
Fax: +81 3 3817 1792
Interests: gene expression analysis; microRNA regulation of target genes; multivariate analysis; feature extraction

Special Issue Information

Dear Colleagues,

MicroRNA is a short non-coding RNA whose primary function is supposed to be post-transcriptional regulation of mRNAs. Although it has been extensively studied for over a decade, its detailed mechanisms have not yet been fully understood. The difficulty is possibly because of lack of experimentally and theoretically effective methods, and this should be solved by invention of new technologies. Thus, any new proposals regarding them are welcomed. In addition to these, many new aspects, e.g., coordinated actions of microRNA with various epigenetic factors, including promoter methylations, histone modifications, and structures of chromosome, have started to pique researchers’ interests. Furthermore, non-canonical functions, e.g., functionalities inside nuclei and non-canonical bindings, also seem to be important. In conclusion, any research papers about new theoretical, computational, or experimental methodologies, as well as excellent reviews regarding these topics are welcomed. MicroRNA regulations, of not only target genes, but also any pathways, diseases, or differentiation, are also interesting topics. We are looking forward to receiving many submissions from outstanding expert on these topics.

Prof. Y-h. Taguchi
Guest Editor

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Keywords

  • microRNA regulation of target genes
  • microRNA regulation of pathways
  • microRNA regulation of diseases
  • coordinated actions with various epigenetic factors
  • microRNA functions inside nuclei

Related Special Issue

Published Papers (43 papers)

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Research

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Open AccessArticle MicroRNAs and Drinking: Association between the Pre-miR-27a rs895819 Polymorphism and Alcohol Consumption in a Mediterranean Population
Int. J. Mol. Sci. 2016, 17(8), 1338; doi:10.3390/ijms17081338
Received: 16 June 2016 / Revised: 9 August 2016 / Accepted: 10 August 2016 / Published: 16 August 2016
PDF Full-text (442 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recently, microRNAs (miRNA) have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol
[...] Read more.
Recently, microRNAs (miRNA) have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol consumption at the population level. Our aim was to investigate the association between a functional polymorphism in the pre-miR-27a (rs895819 A>G) gene and alcohol consumption in an elderly population. We undertook a cross-sectional study of PREvención con DIeta MEDiterránea (PREDIMED)-Valencia participants (n = 1007, including men and women aged 67 ± 7 years) and measured their alcohol consumption (total and alcoholic beverages) through a validated questionnaire. We found a strong association between the pre-miR-27a polymorphism and total alcohol intake, this being higher in GG subjects (5.2 ± 0.4 in AA, 5.9 ± 0.5 in AG and 9.1 ± 1.8 g/day in GG; padjusted = 0.019). We also found a statistically-significant association of the pre-miR-27a polymorphism with the risk of having a high alcohol intake (>2 drinks/day in men and >1 in women): 5.9% in AA versus 17.5% in GG; padjusted < 0.001. In the sensitivity analysis, this association was homogeneous for sex, obesity and Mediterranean diet adherence. In conclusion, we report for the first time a significant association between a miRNA polymorphism (rs895819) and daily alcohol consumption. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer
Int. J. Mol. Sci. 2016, 17(8), 1298; doi:10.3390/ijms17081298
Received: 20 May 2016 / Revised: 29 July 2016 / Accepted: 4 August 2016 / Published: 10 August 2016
Cited by 6 | PDF Full-text (3366 KB) | HTML Full-text | XML Full-text
Abstract
Metformin, a drug approved for diabetes type II treatment, has been associated with a reduction in the incidence of breast cancer and metastasis and increased survival in diabetic breast cancer patients. High levels of miR-26a expression have been proposed as one of the
[...] Read more.
Metformin, a drug approved for diabetes type II treatment, has been associated with a reduction in the incidence of breast cancer and metastasis and increased survival in diabetic breast cancer patients. High levels of miR-26a expression have been proposed as one of the possible mechanisms for this effect; likewise, this miRNA has also been associated with survival/apoptosis processes in breast cancer. Our aim was to evaluate if miR-26a and some of its targets could mediate the effect of metformin in breast cancer. The viability of MDA-MB-231, MDA-MB-468, and MCF-7 breast cancer cell lines was evaluated with an MTT assay after ectopic overexpression and/or downregulation of miR-26a. Similarly, the expression levels of the miR-26a targets CASP3, CCNE2, ABL2, APAF1, XIAP, BCL-2, PTEN, p53, E2F3, CDC25A, BCL2L1, MCL-1, EZH2, and MTDH were assessed by quantitative polymerase chain reaction (PCR). The effect of metformin treatment on breast cancer cell viability and miR-26a, BCL-2, PTEN, MCL-1, EZH2, and MTDH modulation were evaluated. Wound healing experiments were performed to analyze the effect of miR-26a and metformin treatment on cell migration. MiR-26a overexpression resulted in a reduction in cell viability that was partially recovered by inhibiting it. E2F3, MCL-1, EZH2, MTDH, and PTEN were downregulated by miR-26a and the PTEN (phosphatase and tensin homolog) protein was also reduced after miR-26a overexpression. Metformin treatment reduced breast cancer cell viability, increased miR-26a expression, and led to a reduction in BCL-2, EZH2, and PTEN expression. miR-26a inhibition partly prevents the metformin viability effect and the PTEN and EZH2 expression reduction. Our results indicate that metformin effectively reduces breast cancer cell viability and suggests that the effects of the drug are mediated by an increase in miR-26a expression and a reduction of its targets, PTEN and EHZ2 Thus, the use of metformin in breast cancer treatment constitutes a promising potential breast cancer therapy. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells
Int. J. Mol. Sci. 2016, 17(7), 1092; doi:10.3390/ijms17071092
Received: 18 March 2016 / Revised: 29 June 2016 / Accepted: 30 June 2016 / Published: 8 July 2016
Cited by 5 | PDF Full-text (5069 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck. Although radiotherapy is used for OSCC treatment, the occurrence of radioresistant cancer cells limits its efficiency. MicroRNAs (miRNAs) are non-coding RNAs with lengths of 18–25 base pairs and known
[...] Read more.
Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck. Although radiotherapy is used for OSCC treatment, the occurrence of radioresistant cancer cells limits its efficiency. MicroRNAs (miRNAs) are non-coding RNAs with lengths of 18–25 base pairs and known to be involved in carcinogenesis. We previously demonstrated that by targeting B lymphoma Mo-MLV insertion region 1 homolog (Bmi1), miR-494-3p functions as a putative tumor suppressor miRNA in OSCC. In this study, we further discovered that miR-494-3p could enhance the radiosensitivity of SAS OSCC cells and induce cellular senescence. The overexpression of miR-494-3p in SAS cells increased the population of senescence-associated β-galactosidase positive cells, the expression of p16INK4a and retinoblastoma 1 (RB1), as well as downregulated Bmi1. The knockdown of Bmi1 by lentiviral-mediated delivery of specific short hairpin RNAs (shRNAs) also enhanced the radiosensitivity of SAS cells and the activation of the senescence pathway. Furthermore, the inverse correlation between Bmi1 and miR-494-3p expression was observed among OSCC tissues. Results suggest that miR-494-3p could increase the radiosensitivity of OSCC cells through the induction of cellular senescence caused by the downregulation of Bmi1. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessArticle MicroRNA-21a-5p Functions on the Regulation of Melanogenesis by Targeting Sox5 in Mouse Skin Melanocytes
Int. J. Mol. Sci. 2016, 17(7), 959; doi:10.3390/ijms17070959
Received: 29 February 2016 / Revised: 2 June 2016 / Accepted: 12 June 2016 / Published: 24 June 2016
Cited by 2 | PDF Full-text (1245 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) play an important role in regulating almost all biological processes. miRNAs bind to the 3′ untranslated region (UTR) of mRNAs by sequence matching. In a previous study, we demonstrated that miR-21 was differently expressed in alpaca skin with different hair color.
[...] Read more.
MicroRNAs (miRNAs) play an important role in regulating almost all biological processes. miRNAs bind to the 3′ untranslated region (UTR) of mRNAs by sequence matching. In a previous study, we demonstrated that miR-21 was differently expressed in alpaca skin with different hair color. However, the molecular and cellular mechanisms for miR-21 to regulate the coat color are not yet completely understood. In this study, we transfected miR-21a-5p into mouse melanocytes and demonstrated its function on melanogenesis of miR-21a-5p by targeting Sox5, which inhibits melanogenesis in mouse melanocytes. The results suggested that miR-21a-5p targeted Sox5 gene based on the binding site in 3′ UTR of Sox5 and overexpression of miR-21a-5p significantly down-regulated Sox5 mRNA and protein expression. Meanwhile, mRNA and protein expression of microphthalmia transcription factor (MITF) and Tyrosinase (TYR) were up-regulated, which subsequently make the melanin production in melanocytes increased. The results suggest that miR-21a-5p regulates melanogenesis via MITF by targeting Sox5. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessArticle Spatial Partitioning of miRNAs Is Related to Sequence Similarity in Overall Transcriptome
Int. J. Mol. Sci. 2016, 17(6), 830; doi:10.3390/ijms17060830
Received: 31 March 2016 / Revised: 12 May 2016 / Accepted: 19 May 2016 / Published: 8 June 2016
Cited by 1 | PDF Full-text (2173 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
RNAs have been shown to exhibit differential enrichment between nuclear, cytoplasmic, and exosome fractions. A current fundamental question asks why non-coding RNA partition into different spatial compartments. We report on the analysis of cellular compartment models with miRNA data sources for spatial-mechanistic modeling
[...] Read more.
RNAs have been shown to exhibit differential enrichment between nuclear, cytoplasmic, and exosome fractions. A current fundamental question asks why non-coding RNA partition into different spatial compartments. We report on the analysis of cellular compartment models with miRNA data sources for spatial-mechanistic modeling to address the broad area of multi-scalar cellular communication by miRNAs. We show that spatial partitioning of miRNAs is related to sequence similarity to the overall transcriptome. This has broad implications in biological informatics for gene regulation and provides a deeper understanding of nucleotide sequence structure and RNA language meaning for human pathologies resulting from changes in gene expression. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessCommunication A Systematic Comparison of Purification and Normalization Protocols for Quantitative MicroRNA Expressional Profiling in Insulin-Producing Cells
Int. J. Mol. Sci. 2016, 17(6), 896; doi:10.3390/ijms17060896
Received: 15 April 2016 / Revised: 12 May 2016 / Accepted: 30 May 2016 / Published: 7 June 2016
PDF Full-text (1780 KB) | HTML Full-text | XML Full-text
Abstract
As microRNAs (miRs) are gaining increasing attention as key regulators of cellular processes, expressional quantification is widely applied. However, in the processing of relatively quantified data, the importance of testing the stability of several reference mRNAs and/or miRs and choosing among these for
[...] Read more.
As microRNAs (miRs) are gaining increasing attention as key regulators of cellular processes, expressional quantification is widely applied. However, in the processing of relatively quantified data, the importance of testing the stability of several reference mRNAs and/or miRs and choosing among these for normalization is often overlooked, potentially leading to biased results. Here, we have optimized the purification of miR-enriched total RNA from pancreatic insulin-producing INS-1 cells. Additionally, we optimized and analyzed miR expression by a qPCR-based microarray and by specific qPCR and tested the stability of candidate reference mRNAs and miRs. Hence, this study gives a widely applicable example on how to easily and systematically test and decide how to normalize miR quantification. We suggest that caution in the interpretation of miR quantification studies that do not comprise stability analysis should be exerted. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse Model
Int. J. Mol. Sci. 2016, 17(6), 895; doi:10.3390/ijms17060895
Received: 15 March 2016 / Revised: 17 May 2016 / Accepted: 18 May 2016 / Published: 7 June 2016
Cited by 3 | PDF Full-text (5254 KB) | HTML Full-text | XML Full-text
Abstract
miR-126 has recently been implicated in modulating angiogenic factors in vascular development. Understandings its biological significance might enable development of therapeutic interventions for diseases like age-related macular degeneration (AMD). We aimed to determine the role of miR-126 in AMD using a laser-induced choroidal
[...] Read more.
miR-126 has recently been implicated in modulating angiogenic factors in vascular development. Understandings its biological significance might enable development of therapeutic interventions for diseases like age-related macular degeneration (AMD). We aimed to determine the role of miR-126 in AMD using a laser-induced choroidal neovascularization (CNV) mouse model. CNV was induced by laser photocoagulation in C57BL/6 mice. The CNV mice were transfected with scrambled miR or miR-126 mimic. The expression of miR-126, vascular endothelial growth factor-A (VEGF-A), Kinase insert domain receptor (KDR) and Sprouty-related EVH1 domain-containing protein 1 (SPRED-1) in ocular tissues were analyzed by qPCR and Western blot. The overexpression effects of miR-126 were also proven on human microvascular endothelial cells (HMECs). miR-126 showed a significant decrease in CNV mice (p < 0.05). Both mRNA and protein levels of VEGF-A, KDR and SPRED-1 were upregulated with CNV; these changes were ameliorated by restoration of miR-126 (p < 0.05). CNV was reduced after miR-126 transfection. Transfection of miR-126 reduced the HMECs 2D-capillary-like tube formation (p < 0.01) and migration (p < 0.01). miR-126 has been shown to be a negative modulator of angiogenesis in the eye. All together these results high lights the therapeutic potential of miR-126 suggests that it may contribute as a putative therapeutic target for AMD in humans. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessCommunication Neonatal Heart-Enriched miR-708 Promotes Differentiation of Cardiac Progenitor Cells in Rats
Int. J. Mol. Sci. 2016, 17(6), 875; doi:10.3390/ijms17060875
Received: 14 April 2016 / Revised: 19 May 2016 / Accepted: 27 May 2016 / Published: 7 June 2016
PDF Full-text (2731 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular disease is becoming the leading cause of death throughout the world. However, adult hearts have limited potential for regeneration after pathological injury, partly due to the quiescent status of stem/progenitor cells. Reactivation of cardiac stem/progenitor cells to create more myocyte progeny is
[...] Read more.
Cardiovascular disease is becoming the leading cause of death throughout the world. However, adult hearts have limited potential for regeneration after pathological injury, partly due to the quiescent status of stem/progenitor cells. Reactivation of cardiac stem/progenitor cells to create more myocyte progeny is one of the key steps in the regeneration of a damaged heart. In this study, miR-708 was identified to be enriched in the neonatal cardiomyocytes of rats, but this has not yet been proven in adult humans. A lower level of miR-708 in c-kit(+) stem/progenitor cells was detected compared to non-progenitors. Overexpression of miR-708 induced cardiomyocyte differentiation of cardiac stem/progenitor cells. This finding strengthened the potential of applying miRNAs in the regeneration of injured hearts, and this indicates that miR-708 could be a novel candidate for treatment of heart diseases. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle Predicting MicroRNA Biomarkers for Cancer Using Phylogenetic Tree and Microarray Analysis
Int. J. Mol. Sci. 2016, 17(5), 773; doi:10.3390/ijms17050773
Received: 23 March 2016 / Revised: 13 May 2016 / Accepted: 16 May 2016 / Published: 19 May 2016
Cited by 3 | PDF Full-text (926 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are shown to be involved in the initiation and progression of cancers in the literature, and the expression of miRNAs is used as an important cancer prognostic tool. The aim of this study is to predict high-confidence miRNA biomarkers for cancer.
[...] Read more.
MicroRNAs (miRNAs) are shown to be involved in the initiation and progression of cancers in the literature, and the expression of miRNAs is used as an important cancer prognostic tool. The aim of this study is to predict high-confidence miRNA biomarkers for cancer. We adopt a method that combines miRNA phylogenetic structure and miRNA microarray data analysis to discover high-confidence miRNA biomarkers for colon, prostate, pancreatic, lung, breast, bladder and kidney cancers. There are 53 miRNAs selected through this method that either have potential to involve a single cancer’s development or to involve several cancers’ development. These miRNAs can be used as high-confidence miRNA biomarkers of these seven investigated cancers for further experiment validation. miR-17, miR-20, miR-106a, miR-106b, miR-92, miR-25, miR-16, miR-195 and miR-143 are selected to involve a single cancer’s development in these seven cancers. They have the potential to be useful miRNA biomarkers when the result can be confirmed by experiments. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle MicroRNA-19b Downregulates Gap Junction Protein Alpha1 and Synergizes with MicroRNA-1 in Viral Myocarditis
Int. J. Mol. Sci. 2016, 17(5), 741; doi:10.3390/ijms17050741
Received: 29 March 2016 / Revised: 7 May 2016 / Accepted: 10 May 2016 / Published: 18 May 2016
Cited by 2 | PDF Full-text (3494 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Viral myocarditis (VMC) is a life-threatening disease that leads to heart failure or cardiac arrhythmia. A large number of researches have revealed that mircroRNAs (miRNAs) participate in the pathological processes of VMC. We previously reported that miR-1 repressed the expression of gap junction
[...] Read more.
Viral myocarditis (VMC) is a life-threatening disease that leads to heart failure or cardiac arrhythmia. A large number of researches have revealed that mircroRNAs (miRNAs) participate in the pathological processes of VMC. We previously reported that miR-1 repressed the expression of gap junction protein α1 (GJA1) in VMC. In this study, miR-19b was found to be significantly upregulated using the microarray analysis in a mouse model of VMC, and overexpression of miR-19b led to irregular beating pattern in human cardiomyocytes derived from the induced pluripotent stem cells (hiPSCs-CMs). The upregulation of miR-19b was associated with decreased GJA1 in vivo. Furthermore, a miR-19b inhibitor increased, while its mimics suppressed the expression of GJA1 in HL-1 cells. When GJA1 was overexpressed, the miR-19b mimics-mediated irregular beating was reversed in hiPSCs-CMs. In addition, the effect of miR-19b on GJA1 was enhanced by miR-1 in a dose-dependent manner. These data suggest miR-19b contributes to irregular beating through regulation of GJA1 by cooperating with miR-1. Based on the present and our previous studies, it could be indicated that miR-19b and miR-1 might be critically involved in cardiac arrhythmia associated with VMC. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle Identification of More Feasible MicroRNA–mRNA Interactions within Multiple Cancers Using Principal Component Analysis Based Unsupervised Feature Extraction
Int. J. Mol. Sci. 2016, 17(5), 696; doi:10.3390/ijms17050696
Received: 19 March 2016 / Revised: 13 April 2016 / Accepted: 27 April 2016 / Published: 10 May 2016
Cited by 8 | PDF Full-text (255 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
MicroRNA(miRNA)–mRNA interactions are important for understanding many biological processes, including development, differentiation and disease progression, but their identification is highly context-dependent. When computationally derived from sequence information alone, the identification should be verified by integrated analyses of mRNA and miRNA expression. The drawback
[...] Read more.
MicroRNA(miRNA)–mRNA interactions are important for understanding many biological processes, including development, differentiation and disease progression, but their identification is highly context-dependent. When computationally derived from sequence information alone, the identification should be verified by integrated analyses of mRNA and miRNA expression. The drawback of this strategy is the vast number of identified interactions, which prevents an experimental or detailed investigation of each pair. In this paper, we overcome this difficulty by the recently proposed principal component analysis (PCA)-based unsupervised feature extraction (FE), which reduces the number of identified miRNA–mRNA interactions that properly discriminate between patients and healthy controls without losing biological feasibility. The approach is applied to six cancers: hepatocellular carcinoma, non-small cell lung cancer, esophageal squamous cell carcinoma, prostate cancer, colorectal/colon cancer and breast cancer. In PCA-based unsupervised FE, the significance does not depend on the number of samples (as in the standard case) but on the number of features, which approximates the number of miRNAs/mRNAs. To our knowledge, we have newly identified miRNA–mRNA interactions in multiple cancers based on a single common (universal) criterion. Moreover, the number of identified interactions was sufficiently small to be sequentially curated by literature searches. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle Prognostic Value of MicroRNAs in Preoperative Treated Rectal Cancer
Int. J. Mol. Sci. 2016, 17(4), 568; doi:10.3390/ijms17040568
Received: 9 February 2016 / Revised: 1 April 2016 / Accepted: 6 April 2016 / Published: 15 April 2016
Cited by 4 | PDF Full-text (1048 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: Patients with locally advanced rectal cancer are treated with preoperative chemoradiotherapy followed by surgical resection. Despite similar clinical parameters (uT2-3, uN+) and standard therapy, patients’ prognoses differ widely. A possible prediction of prognosis through microRNAs as biomarkers out of treatment-naïve biopsies would
[...] Read more.
Background: Patients with locally advanced rectal cancer are treated with preoperative chemoradiotherapy followed by surgical resection. Despite similar clinical parameters (uT2-3, uN+) and standard therapy, patients’ prognoses differ widely. A possible prediction of prognosis through microRNAs as biomarkers out of treatment-naïve biopsies would allow individualized therapy options. Methods: Microarray analysis of 45 microdissected preoperative biopsies from patients with rectal cancer was performed to identify potential microRNAs to predict overall survival, disease-free survival, cancer-specific survival, distant-metastasis-free survival, tumor regression grade, or nodal stage. Quantitative real-time polymerase chain reaction (qPCR) was performed on an independent set of 147 rectal cancer patients to validate relevant miRNAs. Results: In the microarray screen, 14 microRNAs were significantly correlated to overall survival. Five microRNAs were included from previous work. Finally, 19 miRNAs were evaluated by qPCR. miR-515-5p, miR-573, miR-579 and miR-802 demonstrated significant correlation with overall survival and cancer-specific survival (p < 0.05). miR-573 was also significantly correlated with the tumor regression grade after preoperative chemoradiotherapy. miR-133b showed a significant correlation with distant-metastasis-free survival. miR-146b expression levels showed a significant correlation with nodal stage. Conclusion: Specific microRNAs can be used as biomarkers to predict prognosis of patients with rectal cancer and possibly stratify patients’ therapy if validated in a prospective study. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessCommunication miRTargetLink—miRNAs, Genes and Interaction Networks
Int. J. Mol. Sci. 2016, 17(4), 564; doi:10.3390/ijms17040564
Received: 25 March 2016 / Revised: 6 April 2016 / Accepted: 7 April 2016 / Published: 14 April 2016
Cited by 9 | PDF Full-text (963 KB) | HTML Full-text | XML Full-text
Abstract
Information on miRNA targeting genes is growing rapidly. For high-throughput experiments, but also for targeted analyses of few genes or miRNAs, easy analysis with concise representation of results facilitates the work of life scientists. We developed miRTargetLink, a tool for automating respective analysis
[...] Read more.
Information on miRNA targeting genes is growing rapidly. For high-throughput experiments, but also for targeted analyses of few genes or miRNAs, easy analysis with concise representation of results facilitates the work of life scientists. We developed miRTargetLink, a tool for automating respective analysis procedures that are frequently applied. Input of the web-based solution is either a single gene or single miRNA, but also sets of genes or miRNAs, can be entered. Validated and predicted targets are extracted from databases and an interaction network is presented. Users can select whether predicted targets, experimentally validated targets with strong or weak evidence, or combinations of those are considered. Central genes or miRNAs are highlighted and users can navigate through the network interactively. To discover the most relevant biochemical processes influenced by the target network, gene set analysis and miRNA set analysis are integrated. As a showcase for miRTargetLink, we analyze targets of five cardiac miRNAs. miRTargetLink is freely available without restrictions at www.ccb.uni-saarland.de/mirtargetlink. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle Characterization of miR-206 Promoter and Its Association with Birthweight in Chicken
Int. J. Mol. Sci. 2016, 17(4), 559; doi:10.3390/ijms17040559
Received: 7 March 2016 / Revised: 5 April 2016 / Accepted: 6 April 2016 / Published: 14 April 2016
PDF Full-text (1182 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
miRNAs have been widely investigated in terms of cell proliferation and differentiation. However, little is known about their effects on bird growth. Here we characterized the promoter of miR-206 in chicken and found that the preferable promoter was located in 1200 bp upstream
[...] Read more.
miRNAs have been widely investigated in terms of cell proliferation and differentiation. However, little is known about their effects on bird growth. Here we characterized the promoter of miR-206 in chicken and found that the preferable promoter was located in 1200 bp upstream of pri-miR-206. In this region, many key transcription factors, including MyoD, c-Myb, CEBPα/β, AP-4, RAP1, Brn2, GATA-1/2/3, E47, Sn, upstream stimulatory factor (USF) and CdxA, were predicted to bind and interact with miR-206 promoter. Overexpression of MyoD sharply increased miR-206 expression in both fibroblast and myoblast cells, and also the regulation in the myoblast cells was much stronger, indicating that miR-206 was regulated by MyoD combined with other muscle specific transcriptional factors. Aiming to further investigate the relationship between miR-206 mutation and transcriptional expression, total of 23 SNPs were identified in the two distinct bird lines by sequencing. Interestingly, the motif bound by MyoD was individually destroyed by G-to-C mutation located at 419 bp upstream of miR-206 precursor. Co-transfecting MyoD and miR-206 promoter in DF-1 cells, the luciferase activity of promoter containing homozygous GG types was significantly higher than CC ones (p < 0.05). Thus, this mutation caused low expression of miR-206. Consistently, eight variants including G-419C mutation exhibited a great effect on birthweight through maker-trait association analysis in F2 population (p < 0.05). Additionally, the regulation of miR-206 on embryo muscle mass mainly by increasing MyoG and muscle creatine kinase (MCK) expression (p < 0.05) with little change in MyoD, TMEM8C and myosin heavy chain (MHC). In conclusion, our findings provide a novel mutation destroying the promoter activity of miR-206 in birds and shed new light to understand the regulation mechanism of miR-206 on the embryonic muscle growth. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessArticle Combining miRNA and mRNA Expression Profiles in Wilms Tumor Subtypes
Int. J. Mol. Sci. 2016, 17(4), 475; doi:10.3390/ijms17040475
Received: 28 January 2016 / Revised: 18 March 2016 / Accepted: 22 March 2016 / Published: 30 March 2016
Cited by 6 | PDF Full-text (1836 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Wilms tumor (WT) is the most common childhood renal cancer. Recent findings of mutations in microRNA (miRNA) processing proteins suggest a pivotal role of miRNAs in WT genesis. We performed miRNA expression profiling of 36 WTs of different subtypes and four normal kidney
[...] Read more.
Wilms tumor (WT) is the most common childhood renal cancer. Recent findings of mutations in microRNA (miRNA) processing proteins suggest a pivotal role of miRNAs in WT genesis. We performed miRNA expression profiling of 36 WTs of different subtypes and four normal kidney tissues using microarrays. Additionally, we determined the gene expression profile of 28 of these tumors to identify potentially correlated target genes and affected pathways. We identified 85 miRNAs and 2107 messenger RNAs (mRNA) differentially expressed in blastemal WT, and 266 miRNAs and 1267 mRNAs differentially expressed in regressive subtype. The hierarchical clustering of the samples, using either the miRNA or mRNA profile, showed the clear separation of WT from normal kidney samples, but the miRNA pattern yielded better separation of WT subtypes. A correlation analysis of the deregulated miRNA and mRNAs identified 13,026 miRNA/mRNA pairs with inversely correlated expression, of which 2844 are potential interactions of miRNA and their predicted mRNA targets. We found significant upregulation of miRNAs-183, -301a/b and -335 for the blastemal subtype, and miRNAs-181b, -223 and -630 for the regressive subtype. We found marked deregulation of miRNAs regulating epithelial to mesenchymal transition, especially in the blastemal subtype, and miRNAs influencing chemosensitivity, especially in regressive subtypes. Further research is needed to assess the influence of preoperative chemotherapy and tumor infiltrating lymphocytes on the miRNA and mRNA patterns in WT. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessArticle MicroRNA Expression during Bovine Oocyte Maturation and Fertilization
Int. J. Mol. Sci. 2016, 17(3), 396; doi:10.3390/ijms17030396
Received: 5 February 2016 / Revised: 3 March 2016 / Accepted: 9 March 2016 / Published: 18 March 2016
Cited by 9 | PDF Full-text (1551 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Successful fertilization and subsequent embryo development rely on complex molecular processes starting with the development of oocyte competence through maturation. MicroRNAs (miRNAs) are small non-coding RNA molecules that function as gene regulators in many biological systems, including the oocyte and embryo. In order
[...] Read more.
Successful fertilization and subsequent embryo development rely on complex molecular processes starting with the development of oocyte competence through maturation. MicroRNAs (miRNAs) are small non-coding RNA molecules that function as gene regulators in many biological systems, including the oocyte and embryo. In order to further explore the roles of miRNAs in oocyte maturation, we employed small RNA sequencing as a screening tool to identify and characterize miRNA populations present in pools of bovine germinal vesicle (GV) oocytes, metaphase II (MII) oocytes, and presumptive zygotes (PZ). Each stage contained a defined miRNA population, some of which showed stable expression while others showed progressive changes between stages that were subsequently confirmed by quantitative reverse transcription polymerase chain reaction (RT-PCR). Bta-miR-155, bta-miR-222, bta-miR-21, bta-let-7d, bta-let-7i, and bta-miR-190a were among the statistically significant differentially expressed miRNAs (p < 0.05). To determine whether changes in specific primary miRNA (pri-miRNA) transcripts were responsible for the observed miRNA changes, we evaluated pri-miR-155, -222 and let-7d expression. Pri-miR-155 and -222 were not detected in GV oocytes but pri-miR-155 was present in MII oocytes, indicating transcription during maturation. In contrast, levels of pri-let-7d decreased during maturation, suggesting that the observed increase in let-7d expression was likely due to processing of the primary transcript. This study demonstrates that both dynamic and stable populations of miRNAs are present in bovine oocytes and zygotes and extend previous studies supporting the importance of the small RNA landscape in the maturing bovine oocyte and early embryo. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessArticle Integrative Analyses of miRNA-mRNA Interactions Reveal let-7b, miR-128 and MAPK Pathway Involvement in Muscle Mass Loss in Sex-Linked Dwarf Chickens
Int. J. Mol. Sci. 2016, 17(3), 276; doi:10.3390/ijms17030276
Received: 18 January 2016 / Revised: 17 February 2016 / Accepted: 17 February 2016 / Published: 24 February 2016
Cited by 3 | PDF Full-text (11606 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle
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The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle fiber diameter. Our previous study has presented the mRNA and miRNA expression profiles of the SLD chicken and normal chicken between embryo day 14 and seven weeks of age. However, the molecular mechanism of GHR-deficient induced muscle mass loss is still unclear, and the key molecules and pathways underlying the GHR-deficient induced muscle mass loss also remain to be illustrated. Here, by functional network analysis of the differentially expressed miRNAs and mRNAs between the SLD and normal chickens, we revealed that let-7b, miR-128 and the MAPK pathway might play key roles in the GHR-deficient induced muscle mass loss, and that the reduced cell division and growth are potential cellular processes during the SLD chicken skeletal muscle development. Additionally, we also found some genes and miRNAs involved in chicken skeletal muscle development, through the MAPK, PI3K-Akt, Wnt and Insulin signaling pathways. This study provides new insights into the molecular mechanism underlying muscle mass loss in the SLD chickens, and some regulatory networks that are crucial for chicken skeletal muscle development. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle Deep Sequencing and Screening of Differentially Expressed MicroRNAs Related to Milk Fat Metabolism in Bovine Primary Mammary Epithelial Cells
Int. J. Mol. Sci. 2016, 17(2), 200; doi:10.3390/ijms17020200
Received: 24 November 2015 / Revised: 19 January 2016 / Accepted: 26 January 2016 / Published: 17 February 2016
Cited by 6 | PDF Full-text (1600 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Milk fat is a key factor affecting milk quality and is also a major trait targeted in dairy cow breeding. To determine how the synthesis and the metabolism of lipids in bovine milk is regulated at the miRNA level, primary mammary epithelial cells
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Milk fat is a key factor affecting milk quality and is also a major trait targeted in dairy cow breeding. To determine how the synthesis and the metabolism of lipids in bovine milk is regulated at the miRNA level, primary mammary epithelial cells (pMEC) derived from two Chinese Holstein dairy cows that produced extreme differences in milk fat percentage were cultured by the method of tissue nubbles culture. Small RNA libraries were constructed from each of the two pMEC groups, and Solexa sequencing and bioinformatics analysis were then used to determine the abundance of miRNAs and their differential expression pattern between pMECs. Target genes and functional prediction of differentially expressed miRNAs by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis illustrated their roles in milk fat metabolism. Results show that a total of 292 known miRNAs and 116 novel miRNAs were detected in both pMECs. Identification of known and novel miRNA candidates demonstrated the feasibility and sensitivity of sequencing at the cellular level. Additionally, 97 miRNAs were significantly differentially expressed between the pMECs. Finally, three miRNAs including bta-miR-33a, bta-miR-152 and bta-miR-224 whose predicted target genes were annotated to the pathway of lipid metabolism were screened and verified by real-time qPCR and Western-blotting experiments. This study is the first comparative profiling of the miRNA transcriptome in pMECs that produce different milk fat content. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle Role of miR-222-3p in c-Src-Mediated Regulation of Osteoclastogenesis
Int. J. Mol. Sci. 2016, 17(2), 240; doi:10.3390/ijms17020240
Received: 15 December 2015 / Revised: 6 February 2016 / Accepted: 6 February 2016 / Published: 16 February 2016
Cited by 3 | PDF Full-text (3591 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that play a mostly post-transcriptional regulatory role in gene expression. Using RAW264.7 pre-osteoclast cells and genome-wide expression analysis, we identified a set of miRNAs that are involved in osteoclastogenesis. Based on in silico analysis, we specifically focused
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MicroRNAs (miRNAs) are small non-coding RNAs that play a mostly post-transcriptional regulatory role in gene expression. Using RAW264.7 pre-osteoclast cells and genome-wide expression analysis, we identified a set of miRNAs that are involved in osteoclastogenesis. Based on in silico analysis, we specifically focused on miR-222-3p and evaluated its role in osteoclastogenesis. The results show that the inhibitor of miR-222-3p upregulated the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and tartrate-resistant acid phosphatase (TRAP), while its mimicking agent downregulated their mRNA levels. Western blot analysis showed that its inhibitor increased the protein levels of TRAP and cathepsin K, while its mimicking agent decreased their levels. Genome-wide mRNA expression analysis in the presence and absence of receptor activator of nuclear factor κ-B ligand (RANKL) predicted c-Src as a potential regulatory target of miR-222-3p. Live cell imaging using a fluorescence resonance energy transfer (FRET) technique revealed that miR-222-3p acted as an inhibitor of c-Src activity, and a partial silencing of c-Src suppressed RANKL-induced expression of TRAP and cathepsin K, as well as the number of multi-nucleated osteoclasts and their pit formation. Collectively, the study herein demonstrates that miR-222-3p serves as an inhibitor of osteoclastogenesis and c-Src mediates its inhibition of cathepsin K and TRAP. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessArticle miR-9-5p, miR-675-5p and miR-138-5p Damages the Strontium and LRP5-Mediated Skeletal Cell Proliferation, Differentiation, and Adhesion
Int. J. Mol. Sci. 2016, 17(2), 236; doi:10.3390/ijms17020236
Received: 1 January 2016 / Revised: 4 February 2016 / Accepted: 5 February 2016 / Published: 15 February 2016
Cited by 5 | PDF Full-text (1998 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study was designed to evaluate the effects of strontium on the expression levels of microRNAs (miRNAs) and to explore their effects on skeletal cell proliferation, differentiation, adhesion, and apoptosis. The targets of these miRNAs were also studied. Molecular cloning, cell proliferation assay,
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This study was designed to evaluate the effects of strontium on the expression levels of microRNAs (miRNAs) and to explore their effects on skeletal cell proliferation, differentiation, adhesion, and apoptosis. The targets of these miRNAs were also studied. Molecular cloning, cell proliferation assay, cell apoptosis assay, quantitative real-time PCR, and luciferase reporter assay were used. Strontium altered the expression levels of miRNAs in vitro and in vivo. miR-9-5p, miR-675-5p, and miR-138-5p impaired skeletal cell proliferation, cell differentiation and cell adhesion. miR-9-5p and miR-675-5p induced MC3T3-E1 cell apoptosis more specifically than miR-138-5p. miR-9-5p, miR-675-5p, and miR-138-5p targeted glycogen synthase kinase 3 β (GSK3β), ATPase Aminophospholipid Transporter Class I Type 8A Member 2 (ATP8A2), and Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (EIF4EBP1), respectively. Low-density lipoprotein receptor-related protein 5 (LRP5) played a positive role in skeletal development. miR-9-5p, miR-675-5p, and miR-138-5p damage strontium and LRP5-mediated skeletal cell proliferation, differentiation, and adhesion, and induce cell apoptosis by targeting GSK3β, ATP8A2, and EIF4EBP1, respectively. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer’s Disease (AD)-Novel and Unique Pathological Features
Int. J. Mol. Sci. 2015, 16(12), 30105-30116; doi:10.3390/ijms161226223
Received: 7 December 2015 / Revised: 12 December 2015 / Accepted: 15 December 2015 / Published: 17 December 2015
Cited by 9 | PDF Full-text (864 KB) | HTML Full-text | XML Full-text
Abstract
Of the approximately ~2.65 × 103 mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset—about 35–40—are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure
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Of the approximately ~2.65 × 103 mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset—about 35–40—are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA–mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer’s disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle miR-29a Participated in Nacre Formation and Immune Response by Targeting Y2R in Pinctada martensii
Int. J. Mol. Sci. 2015, 16(12), 29436-29445; doi:10.3390/ijms161226182
Received: 17 September 2015 / Revised: 26 November 2015 / Accepted: 1 December 2015 / Published: 10 December 2015
Cited by 3 | PDF Full-text (2663 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
miR-29a is a conserved miRNA that participates in bone formation and immune response in vertebrates. miR-29a of Pinctada martensii (Pm-miR-29a) was identified in the previous research though deep sequencing. In this report, the precise sequence of mature Pm-miR-29a was validated using miRNA rapid
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miR-29a is a conserved miRNA that participates in bone formation and immune response in vertebrates. miR-29a of Pinctada martensii (Pm-miR-29a) was identified in the previous research though deep sequencing. In this report, the precise sequence of mature Pm-miR-29a was validated using miRNA rapid amplification of cDNA ends (miR-RACE) technology. The precursor sequence of Pm-miR-29a was predicted to have 87 bp. Stem loop qRT-PCR analysis showed that Pm-miR-29a was easily detected in all the tissues, although expressions in the mantle and gill were low. The microstructure showed the disrupted growth of the nacre after Pm-miR-29a over-expression, which was induced by mimic injection into P. martensii. Results of the target analysis indicated that neuropeptide Y receptor type 2 (Y2R) was the potential target of Pm-miR-29a. Meanwhile, Pm-miR-29a mimics could obviously inhibit the relative luciferase activity of the reporter containing 3′ UTR (Untranslated Regions) of the Y2R gene. Furthermore, the expression of Y2R was downregulated whereas expressions of interleukin 17 (IL-17) and nuclear factor κB (NF-κB) were upregulated after Pm-miR-29a over-expression in the mantle and gill, thereby suggesting that Pm-miR-29a could activate the immune response of the pearl oyster. Results showed that Pm-miR-29a was involved in nacre formation and immune response by regulating Y2R in pearl oyster P. martensii. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle gga-miR-101-3p Plays a Key Role in Mycoplasma gallisepticum (HS Strain) Infection of Chicken
Int. J. Mol. Sci. 2015, 16(12), 28669-28682; doi:10.3390/ijms161226121
Received: 28 October 2015 / Revised: 22 November 2015 / Accepted: 24 November 2015 / Published: 2 December 2015
Cited by 3 | PDF Full-text (6084 KB) | HTML Full-text | XML Full-text
Abstract
Mycoplasma gallisepticum (MG), one of the most pathogenic Mycoplasma, has caused tremendous economic loss in the poultry industry. Recently, increasing evidence has suggested that micro ribonucleic acids (miRNAs) are involved in microbial pathogenesis. However, little is known about potential roles of miRNAs
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Mycoplasma gallisepticum (MG), one of the most pathogenic Mycoplasma, has caused tremendous economic loss in the poultry industry. Recently, increasing evidence has suggested that micro ribonucleic acids (miRNAs) are involved in microbial pathogenesis. However, little is known about potential roles of miRNAs in MG infection of chicken. In the present study, using miRNA Solexa sequencing we have found that gga-miR-101-3p was up-regulated in the lungs of MG-infected chicken embryos. Moreover, gga-miR-101-3p regulated expression of the host enhancer of zeste homolog 2 (EZH2) through binding to the 3’ un-translated region (3’-UTR) of EZH2 gene. Over-expression of gga-miR-101-3p significantly inhibited EZH2 expression and hence inhibited proliferation of chicken embryonic fibroblast (DF-1 cells) by blocking the G1-to-S phase transition. Similar results were obtained in MG-infected chicken embryos and DF-1 cells, where gga-miR-101-3p was significantly up-regulated, while EZH2 was significantly down-regulated. This study reveals that gga-miR-101-3p plays an important role in MG infection through regulation of EZH2 expression and provides a new insight into the mechanisms of MG pathogenesis. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessArticle miR-218 Inhibits Erythroid Differentiation and Alters Iron Metabolism by Targeting ALAS2 in K562 Cells
Int. J. Mol. Sci. 2015, 16(12), 28156-28168; doi:10.3390/ijms161226088
Received: 9 October 2015 / Revised: 13 November 2015 / Accepted: 17 November 2015 / Published: 26 November 2015
Cited by 1 | PDF Full-text (3779 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
microRNAs (miRNAs) are involved in a variety of biological processes. The regulatory function and potential role of miRNAs targeting the mRNA of the 5′-aminolevulinate synthase 2 (ALAS2) in erythropoiesis were investigated in order to identify miRNAs which play a role in
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microRNAs (miRNAs) are involved in a variety of biological processes. The regulatory function and potential role of miRNAs targeting the mRNA of the 5′-aminolevulinate synthase 2 (ALAS2) in erythropoiesis were investigated in order to identify miRNAs which play a role in erythroid iron metabolism and differentiation. Firstly, the role of ALAS2 in erythroid differentiation and iron metabolism in human erythroid leukemia cells (K562) was confirmed by ALAS2 knockdown. Through a series of screening strategies and experimental validations, it was identified that hsa-miR-218 (miR-218) targets and represses the expression of ALAS2 by binding to the 3′-untranslated region (UTR). Overexpression of miR-218 repressed erythroid differentiation and altered iron metabolism in K562 cells similar to that seen in the ALAS2 knockdown in K562 cells. In addition to iron metabolism and erythroid differentiation, miR-218 was found to be responsible for a reduction in K562 cell growth. Taken together, our results show that miR-218 inhibits erythroid differentiation and alters iron metabolism by targeting ALAS2 in K562 cells. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle MiR542-3p Regulates the Epithelial-Mesenchymal Transition by Directly Targeting BMP7 in NRK52e
Int. J. Mol. Sci. 2015, 16(11), 27945-27955; doi:10.3390/ijms161126075
Received: 24 October 2015 / Revised: 13 November 2015 / Accepted: 16 November 2015 / Published: 24 November 2015
Cited by 2 | PDF Full-text (2950 KB) | HTML Full-text | XML Full-text
Abstract
Accumulating evidence demonstrated that miRNAs are highly involved in kidney fibrosis and Epithelial-Eesenchymal Transition (EMT), however, the mechanisms of miRNAs in kidney fibrosis are poorly understood. In this work, we identified that miR542-3p could promote EMT through down-regulating bone morphogenetic protein 7 (BMP7)
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Accumulating evidence demonstrated that miRNAs are highly involved in kidney fibrosis and Epithelial-Eesenchymal Transition (EMT), however, the mechanisms of miRNAs in kidney fibrosis are poorly understood. In this work, we identified that miR542-3p could promote EMT through down-regulating bone morphogenetic protein 7 (BMP7) expression by targeting BMP7 3′UTR. Firstly, real-time PCR results showed that miR542-3p was significantly up-regulated in kidney fibrosis in vitro and in vivo. Moreover, Western blot results demonstrated that miR542-3p may promote EMT in the NRK52e cell line. In addition, we confirmed that BMP7, which played a crucial role in anti-kidney fibrosis and suppressed the progression of EMT, was a target of miR542-3p through Dual-Luciferase reporter assay, as did Western blot analysis. The effects of miR542-3p on regulating EMT could also be suppressed by transiently overexpressing BMP7 in NRK52e cells. Taken together, miR542-3p may be a critical mediator of the induction of EMT via directly targeting BMP7. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle Identification and Functional Analysis of MicroRNAs in Mice following Focal Cerebral Ischemia Injury
Int. J. Mol. Sci. 2015, 16(10), 24302-24318; doi:10.3390/ijms161024302
Received: 6 August 2015 / Revised: 9 September 2015 / Accepted: 10 September 2015 / Published: 14 October 2015
Cited by 7 | PDF Full-text (3117 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Numerous studies have demonstrated that genes, RNAs, and proteins are involved in the occurrence and development of stroke. In addition, previous studies concluded that microRNAs (miRNAs or miRs) are closely related to the pathological process of ischemic and hypoxic disease. Therefore, the aims
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Numerous studies have demonstrated that genes, RNAs, and proteins are involved in the occurrence and development of stroke. In addition, previous studies concluded that microRNAs (miRNAs or miRs) are closely related to the pathological process of ischemic and hypoxic disease. Therefore, the aims of this study were to quantify the altered expression levels of miRNAs in the infarct region 6 h after middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in mice using a large-scale miRNAs microarray. Firstly, MCAO-induced cerebral ischemic injuries were investigated by observing the changes of neurological deficits, infarct volume and edema ratio. One hundred and eighteen differentially expressed miRNAs were identified in the infarct region of mice following the MCAOs compared with sham group (p < 0.05 was considered as significant). Among these 118 significantly expressed microRNAs, we found that 12 miRNAs were up-regulated with fold changes lager than two, and 18 miRNAs were down-regulated with fold changes less than 0.5 in the infarct region of mice following the 6 h MCAOs, compared with the sham group. Then, these 30 miRNAs with expression in fold change larger than two or less than 0.5 was predicted, and the functions of the target genes of 30 miRNAs were analyzed using a bioinformatics method. Finally, the miRNA-gene network was established and the functional miRNA-mRNA pairs were identified, which provided insight into the roles of the specific miRNAs that regulated specified genes in the ischemic injuries. The miRNAs identified in this study may represent effective therapeutic targets for stroke, and further study of the role of these targets may increase our understanding of the mechanisms underlying ischemic injuries. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessArticle MiR-30a Inhibits the Epithelial—Mesenchymal Transition of Podocytes through Downregulation of NFATc3
Int. J. Mol. Sci. 2015, 16(10), 24032-24047; doi:10.3390/ijms161024032
Received: 8 August 2015 / Revised: 31 August 2015 / Accepted: 29 September 2015 / Published: 12 October 2015
Cited by 6 | PDF Full-text (3009 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) possess an important regulating effect among numerous renal diseases, while their functions in the process of epithelial-to-mesenchymal transition (EMT) after podocyte injury remain unclear. The purpose of our study is to identify the potential functions of miR-30a in EMT of podocytes
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MicroRNAs (miRNAs) possess an important regulating effect among numerous renal diseases, while their functions in the process of epithelial-to-mesenchymal transition (EMT) after podocyte injury remain unclear. The purpose of our study is to identify the potential functions of miR-30a in EMT of podocytes and explore the underlying mechanisms of miR-30a in the impaired podocytes. The results revealed that downregulation of miR-30a in podocyte injury animal models and patients, highly induced the mesenchymal markers of EMT including Collagen I, Fibronectin and Snail. Furthermore, overexpression of miR-30a enhances epithelial markers (E-cadherin) but diminished mesenchymal markers (Collagen I, Fibronectin and Snail) in podocytes. In addition, we established miR-30a target NFATc3, an important transcription factor of Non-canonical Wnt signaling pathway. More importantly, our findings demonstrated that the augmentation of miR-30a level in podocytes inhibits the nuclear translocation of NFATc3 to protect cytoskeleton disorder or rearrangement. In summary, we uncovered the protective function of miR30a targeting NFATc3 in the regulation of podocyte injury response to EMT. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle MicroRNA-302b Enhances the Sensitivity of Hepatocellular Carcinoma Cell Lines to 5-FU via Targeting Mcl-1 and DPYD
Int. J. Mol. Sci. 2015, 16(10), 23668-23682; doi:10.3390/ijms161023668
Received: 7 July 2015 / Revised: 24 August 2015 / Accepted: 1 September 2015 / Published: 6 October 2015
Cited by 5 | PDF Full-text (1856 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
MiR-302b is a member of miR-302-367 cluster. The miR-302-367 cluster played important roles in maintaining pluripotency in human embryonic stem cells (hESCs) and has been proved to be capable of suppressing cell growth in several types of cancer cell lines including Hepatocellular Carcinoma
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MiR-302b is a member of miR-302-367 cluster. The miR-302-367 cluster played important roles in maintaining pluripotency in human embryonic stem cells (hESCs) and has been proved to be capable of suppressing cell growth in several types of cancer cell lines including Hepatocellular Carcinoma (HCC) Cell lines. However, the role that miR-302b plays in the 5-Fluorouracil (5-FU) sensitivity of HCC has not been known. This study showed that miR-302b could enhance the sensitivity to 5-FU in HCC cell lines and verified its two putative targeted genes responsible for its 5-FU sensitivity. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle Analysis of MicroRNA Expression Profiles in Weaned Pig Skeletal Muscle after Lipopolysaccharide Challenge
Int. J. Mol. Sci. 2015, 16(9), 22438-22455; doi:10.3390/ijms160922438
Received: 12 August 2015 / Revised: 3 September 2015 / Accepted: 7 September 2015 / Published: 16 September 2015
Cited by 5 | PDF Full-text (6152 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
MicroRNAs (miRNAs) constitute a class of non-coding RNAs that play a crucial regulatory role in skeletal muscle development and disease. Several acute inflammation conditions including sepsis and cancer are characterized by a loss of skeletal muscle due primarily to excessive muscle catabolism. As
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MicroRNAs (miRNAs) constitute a class of non-coding RNAs that play a crucial regulatory role in skeletal muscle development and disease. Several acute inflammation conditions including sepsis and cancer are characterized by a loss of skeletal muscle due primarily to excessive muscle catabolism. As a well-known inducer of acute inflammation, a lipopolysaccharide (LPS) challenge can cause serious skeletal muscle wasting. However, knowledge of the role of miRNAs in the course of inflammatory muscle catabolism is still very limited. In this study, RNA extracted from the skeletal muscle of pigs injected with LPS or saline was subjected to small RNA deep sequencing. We identified 304 conserved and 114 novel candidate miRNAs in the pig. Of these, four were significantly increased in the LPS-challenged samples and five were decreased. The expression of five miRNAs (ssc-miR-146a-5p, ssc-miR-221-5p, ssc-miR-148b-3p, ssc-miR-215 and ssc-miR-192) were selected for validation by quantitative polymerase chain reaction (qPCR), which found that ssc-miR-146a-5p and ssc-miR-221-5p were significantly upregulated in LPS-challenged pig skeletal muscle. Moreover, we treated mouse C2C12 myotubes with 1000 ng/mL LPS as an acute inflammation cell model. Expression of TNF-α, IL-6, muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) mRNA was strongly induced by LPS. Importantly, miR-146a-5p and miR-221-5p also showed markedly increased expression in LPS-treated C2C12 myotubes, suggesting the two miRNAs may be involved in muscle catabolism systems in response to acute inflammation caused by a LPS challenge. To our knowledge, this study is the first to examine miRNA expression profiles in weaned pig skeletal muscle challenged with LPS, and furthers our understanding of miRNA function in the regulation of inflammatory muscle catabolism. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle MiR-122 Induces Radiosensitization in Non-Small Cell Lung Cancer Cell Line
Int. J. Mol. Sci. 2015, 16(9), 22137-22150; doi:10.3390/ijms160922137
Received: 6 July 2015 / Revised: 27 August 2015 / Accepted: 27 August 2015 / Published: 14 September 2015
Cited by 9 | PDF Full-text (3217 KB) | HTML Full-text | XML Full-text
Abstract
MiR-122 is a novel tumor suppresser and its expression induces cell cycle arrest, or apoptosis, and inhibits cell proliferation in multiple cancer cells, including non-small cell lung cancer (NSCLC) cells. Radioresistance of cancer cell leads to the major drawback of radiotherapy for NSCLC
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MiR-122 is a novel tumor suppresser and its expression induces cell cycle arrest, or apoptosis, and inhibits cell proliferation in multiple cancer cells, including non-small cell lung cancer (NSCLC) cells. Radioresistance of cancer cell leads to the major drawback of radiotherapy for NSCLC and the induction of radiosensitization could be a useful strategy to fix this problem. The present work investigates the function of miR-122 in inducing radiosensitization in A549 cell, a type of NSCLC cells. MiR-122 induces the radiosensitization of A549 cells. MiR-122 also boosts the inhibitory activity of ionizing radiation (IR) on cancer cell anchor-independent growth and invasion. Moreover, miR-122 reduced the expression of its targeted genes related to tumor-survival or cellular stress response. These results indicate that miR-122 would be a novel strategy for NSCLC radiation-therapy. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Review

Jump to: Research

Open AccessReview MicroRNAs in Valvular Heart Diseases: Potential Role as Markers and Actors of Valvular and Cardiac Remodeling
Int. J. Mol. Sci. 2016, 17(7), 1120; doi:10.3390/ijms17071120
Received: 21 April 2016 / Revised: 4 July 2016 / Accepted: 8 July 2016 / Published: 13 July 2016
Cited by 10 | PDF Full-text (1273 KB) | HTML Full-text | XML Full-text
Abstract
miRNAs are a class of over 5000 noncoding RNAs that regulate more than half of the protein-encoding genes by provoking their degradation or preventing their translation. miRNAs are key regulators of complex biological processes underlying several cardiovascular disorders, including left ventricular hypertrophy, ischemic
[...] Read more.
miRNAs are a class of over 5000 noncoding RNAs that regulate more than half of the protein-encoding genes by provoking their degradation or preventing their translation. miRNAs are key regulators of complex biological processes underlying several cardiovascular disorders, including left ventricular hypertrophy, ischemic heart disease, heart failure, hypertension and arrhythmias. Moreover, circulating miRNAs herald promise as biomarkers in acute myocardial infarction and heart failure. In this context, this review gives an overview of studies that suggest that miRNAs could also play a role in valvular heart diseases. This area of research is still at its infancy, and further investigations in large patient cohorts and cellular or animal models are needed to provide strong data. Most studies focused on aortic stenosis, one of the most common valvular diseases in developed countries. Profiling and functional analyses indicate that miRNAs could contribute to activation of aortic valve interstitial cells to a myofibroblast phenotype, leading to valvular fibrosis and calcification, and to pressure overload-induced myocardial remodeling and hypertrophy. Data also indicate that specific miRNA signatures, in combination with clinical and functional imaging parameters, could represent useful biomarkers of disease progression or recovery after aortic valve replacement. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessReview RNA Secondary Structure Modulates FMRP’s Bi-Functional Role in the MicroRNA Pathway
Int. J. Mol. Sci. 2016, 17(6), 985; doi:10.3390/ijms17060985
Received: 17 March 2016 / Revised: 23 May 2016 / Accepted: 14 June 2016 / Published: 22 June 2016
Cited by 4 | PDF Full-text (1602 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs act by post-transcriptionally regulating the gene expression of 30%–60% of mammalian genomes. MicroRNAs are key regulators in all cellular processes, though the mechanism by which the cell activates or represses microRNA-mediated translational regulation is poorly understood. In this review, we discuss the
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MicroRNAs act by post-transcriptionally regulating the gene expression of 30%–60% of mammalian genomes. MicroRNAs are key regulators in all cellular processes, though the mechanism by which the cell activates or represses microRNA-mediated translational regulation is poorly understood. In this review, we discuss the RNA binding protein Fragile X Mental Retardation Protein (FMRP) and its role in microRNA-mediated translational regulation. Historically, FMRP is known to function as a translational suppressor. However, emerging data suggests that FMRP has both an agonistic and antagonistic role in regulating microRNA-mediated translational suppression. This bi-functional role is dependent on FMRP’s interaction with the RNA helicase Moloney leukemia virus 10 (MOV10), which modifies the structural landscape of bound mRNA, therefore facilitating or inhibiting its association with the RNA-Induced Silencing Complex. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessReview Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer
Int. J. Mol. Sci. 2016, 17(6), 945; doi:10.3390/ijms17060945
Received: 2 April 2016 / Revised: 1 June 2016 / Accepted: 7 June 2016 / Published: 16 June 2016
Cited by 23 | PDF Full-text (330 KB) | HTML Full-text | XML Full-text
Abstract
Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and
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Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessReview The Role of miRNA in Papillary Thyroid Cancer in the Context of miRNA Let-7 Family
Int. J. Mol. Sci. 2016, 17(6), 909; doi:10.3390/ijms17060909
Received: 14 April 2016 / Revised: 22 May 2016 / Accepted: 3 June 2016 / Published: 15 June 2016
Cited by 4 | PDF Full-text (408 KB) | HTML Full-text | XML Full-text
Abstract
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. RET/PTC rearrangement is the most common genetic modification identified in this category of cancer, increasing proliferation and dedifferentiation by the activation of the RET/PTC-RAS-BRAF-MAPK-ERK signaling pathway. Recently, let-7 miRNA was found to reduce
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Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. RET/PTC rearrangement is the most common genetic modification identified in this category of cancer, increasing proliferation and dedifferentiation by the activation of the RET/PTC-RAS-BRAF-MAPK-ERK signaling pathway. Recently, let-7 miRNA was found to reduce RAS levels, acting as a tumor suppressor gene. Circulating miRNA profiles of the let-7 family may be used as novel noninvasive diagnostic, prognostic, treatment and surveillance markers for PTC. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessReview The MicroRNA-21 in Autoimmune Diseases
Int. J. Mol. Sci. 2016, 17(6), 864; doi:10.3390/ijms17060864
Received: 10 April 2016 / Revised: 18 May 2016 / Accepted: 30 May 2016 / Published: 3 June 2016
Cited by 6 | PDF Full-text (203 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune
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MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune diseases and may play an essential role in regulating autoimmune responses. In particular, miR-21 promotes Th17 cell differentiation, which mediates the development of multiple autoimmune diseases. In this article, we review the current research on the mechanisms that regulate miR-21 expression, the potential of miR-21 as a diagnostic biomarker for autoimmune disease and the mechanisms by which miR-21 promotes the development of autoimmune disease. We also discussed the therapeutic potential of targeting miR-21 in treating patients with autoimmune disease. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessReview MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases
Int. J. Mol. Sci. 2016, 17(6), 842; doi:10.3390/ijms17060842
Received: 2 April 2016 / Revised: 20 May 2016 / Accepted: 23 May 2016 / Published: 28 May 2016
Cited by 16 | PDF Full-text (1680 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are a class of small, well-conserved noncoding RNAs that regulate gene expression post-transcriptionally. They have been demonstrated to regulate a lot of biological pathways and cellular functions. Many miRNAs are dynamically regulated during central nervous system (CNS) development and are spatially
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MicroRNAs (miRNAs) are a class of small, well-conserved noncoding RNAs that regulate gene expression post-transcriptionally. They have been demonstrated to regulate a lot of biological pathways and cellular functions. Many miRNAs are dynamically regulated during central nervous system (CNS) development and are spatially expressed in adult brain indicating their essential roles in neural development and function. In addition, accumulating evidence strongly suggests that dysfunction of miRNAs contributes to neurological diseases. These observations, together with their gene regulation property, implicated miRNAs to be the key regulators in the complex genetic network of the CNS. In this review, we first focus on the ways through which miRNAs exert the regulatory function and how miRNAs are regulated in the CNS. We then summarize recent findings that highlight the versatile roles of miRNAs in normal CNS physiology and their association with several types of neurological diseases. Subsequently we discuss the limitations of miRNAs research based on current studies as well as the potential therapeutic applications and challenges of miRNAs in neurological disorders. We endeavor to provide an updated description of the regulatory roles of miRNAs in normal CNS functions and pathogenesis of neurological diseases. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessReview The miRacle in Pancreatic Cancer by miRNAs: Tiny Angels or Devils in Disease Progression
Int. J. Mol. Sci. 2016, 17(6), 809; doi:10.3390/ijms17060809
Received: 25 March 2016 / Revised: 4 May 2016 / Accepted: 19 May 2016 / Published: 26 May 2016
Cited by 5 | PDF Full-text (1203 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with increasing incidence and high mortality. Surgical resection is the only potentially curative treatment of patients with PDAC. Because of the late presentation of the disease, about 20 percent of patients are candidates for this
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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with increasing incidence and high mortality. Surgical resection is the only potentially curative treatment of patients with PDAC. Because of the late presentation of the disease, about 20 percent of patients are candidates for this treatment. The average survival of resected patients is between 12 and 20 months, with a high probability of relapse. Standard chemo and radiation therapies do not offer significant improvement of the survival of these patients. Furthermore, novel treatment options aimed at targeting oncogenes or growth factors in pancreatic cancer have proved unsuccessful. Thereby, identifying new biomarkers that can detect early stages of this disease is of critical importance. Among these biomarkers, microRNAs (miRNAs) have supplied a profitable recourse and become an attractive focus of research in PDAC. MiRNAs regulate many genes involved in the development of PDAC through mRNA degradation or translation inhibition. The possibility of intervention in the molecular mechanisms of miRNAs regulation could begin a new generation of PDAC therapies. This review summarizes the reports describing miRNAs involvement in cellular processes involving pancreatic carcinogenesis and their utility in diagnosis, survival and therapeutic potential in pancreatic cancer. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessReview Functions of miRNAs during Mammalian Heart Development
Int. J. Mol. Sci. 2016, 17(5), 789; doi:10.3390/ijms17050789
Received: 30 March 2016 / Revised: 26 April 2016 / Accepted: 13 May 2016 / Published: 21 May 2016
Cited by 4 | PDF Full-text (198 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) play essential roles during mammalian heart development and have emerged as attractive therapeutic targets for cardiovascular diseases. The mammalian embryonic heart is mainly derived from four major cell types during development. These include cardiomyocytes, endocardial cells, epicardial cells, and neural crest
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MicroRNAs (miRNAs) play essential roles during mammalian heart development and have emerged as attractive therapeutic targets for cardiovascular diseases. The mammalian embryonic heart is mainly derived from four major cell types during development. These include cardiomyocytes, endocardial cells, epicardial cells, and neural crest cells. Recent data have identified various miRNAs as critical regulators of the proper differentiation, proliferation, and survival of these cell types. In this review, we briefly introduce the contemporary understanding of mammalian cardiac development. We also focus on recent developments in the field of cardiac miRNAs and their functions during the development of different cell types. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessReview MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis
Int. J. Mol. Sci. 2016, 17(5), 754; doi:10.3390/ijms17050754
Received: 31 March 2016 / Revised: 27 April 2016 / Accepted: 11 May 2016 / Published: 18 May 2016
Cited by 13 | PDF Full-text (616 KB) | HTML Full-text | XML Full-text
Abstract
The process of metabolic re-programing is linked to the activation of oncogenes and/or suppression of tumour suppressor genes, which are regulated by microRNAs (miRNAs). The interplay between oncogenic transformation-driven metabolic re-programming and modulation of aberrant miRNAs further established their critical role in the
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The process of metabolic re-programing is linked to the activation of oncogenes and/or suppression of tumour suppressor genes, which are regulated by microRNAs (miRNAs). The interplay between oncogenic transformation-driven metabolic re-programming and modulation of aberrant miRNAs further established their critical role in the initiation, promotion and progression of cancer by creating a tumorigenesis-prone microenvironment, thus orchestrating processes of evasion to apoptosis, angiogenesis and invasion/migration, as well metastasis. Given the involvement of miRNAs in tumour development and their global deregulation, they may be perceived as biomarkers in cancer of therapeutic relevance. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessReview Managing Pancreatic Adenocarcinoma: A Special Focus in MicroRNA Gene Therapy
Int. J. Mol. Sci. 2016, 17(5), 718; doi:10.3390/ijms17050718
Received: 21 March 2016 / Revised: 6 May 2016 / Accepted: 6 May 2016 / Published: 13 May 2016
Cited by 6 | PDF Full-text (273 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic cancer is an aggressive disease and the fourth most lethal cancer in developed countries. Despite all progress in medicine and in understanding the molecular mechanisms of carcinogenesis, pancreatic cancer still has a poor prognosis, the median survival after diagnosis being around 3
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Pancreatic cancer is an aggressive disease and the fourth most lethal cancer in developed countries. Despite all progress in medicine and in understanding the molecular mechanisms of carcinogenesis, pancreatic cancer still has a poor prognosis, the median survival after diagnosis being around 3 to 6 months and the survival rate of 5 years being less than 4%. For pancreatic ductal adenocarcinoma (PDAC), which represents more than 90% of new pancreatic cancer cases, the prognosis is worse than for the other cancers with a patient mortality of approximately 99%. Therefore, there is a pressing need for developing new and efficient therapeutic strategies for pancreatic cancer. In this regard, microRNAs not only have been seen as potential diagnostic and prognostic molecular markers but also as promising therapeutic agents. In this context, this review provides an examination of the most frequently deregulated microRNAs (miRNAs) in PDAC and their putative molecular targets involved in the signaling pathways of pancreatic
carcinogenesis. Additionally, it is presented a summary of gene therapy clinical trials involving miRNAs and it is illustrated the therapeutic potential associated to these small non-coding RNAs, for PDAC treatment. The facts presented here constitute a strong evidence of the remarkable opportunity associated to the application of microRNA-based therapeutic strategies as a novel approach for cancer therapy. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessReview Is the Efficiency of RNA Silencing Evolutionarily Regulated?
Int. J. Mol. Sci. 2016, 17(5), 719; doi:10.3390/ijms17050719
Received: 12 April 2016 / Revised: 6 May 2016 / Accepted: 9 May 2016 / Published: 12 May 2016
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Abstract
Small interfering RNAs (siRNAs) and microRNAs (miRNAs) regulate gene expression in a sequence-specific manner. Genes with partial complementarity to siRNA/miRNA sequences in their 3′-untranslated regions (UTRs) are suppressed by a mechanism referred to as the siRNA off-target effect or miRNA-mediated RNA silencing. However,
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Small interfering RNAs (siRNAs) and microRNAs (miRNAs) regulate gene expression in a sequence-specific manner. Genes with partial complementarity to siRNA/miRNA sequences in their 3′-untranslated regions (UTRs) are suppressed by a mechanism referred to as the siRNA off-target effect or miRNA-mediated RNA silencing. However, the determinants of such RNA silencing efficiency are poorly understood. Previously, I and co-workers reported that the efficiency of RNA silencing is strongly correlated with the thermodynamic stability of base pairing in the duplex formed within an siRNA/miRNA and between the seed region and its target mRNA. In this review, I first summarize our previous studies that identified the thermodynamic parameter to estimate the silencing efficiency using the calculated base pairing stability: siRNAs downregulate the expression of off-target genes depending on the stability of binding between the siRNA seed region (nucleotides 2–8) and off-target mRNAs, and miRNAs downregulate target mRNA expression depending on the stability of the duplex formed between the 5′ terminus of the miRNA and its target mRNA. I further discuss the possibility that such thermodynamic features of silencing efficiency may have arisen during evolution with increasing body temperature in various organisms. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessReview MicroRNA in United Airway Diseases
Int. J. Mol. Sci. 2016, 17(5), 716; doi:10.3390/ijms17050716
Received: 1 April 2016 / Revised: 2 May 2016 / Accepted: 5 May 2016 / Published: 12 May 2016
Cited by 4 | PDF Full-text (618 KB) | HTML Full-text | XML Full-text
Abstract
The concept of united airway diseases (UAD) has received increasing attention in recent years. Sustained and increased inflammation is a common feature of UAD, which is inevitably accompanied with marked gene modification and tight gene regulation. However, gene regulation in the common inflammatory
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The concept of united airway diseases (UAD) has received increasing attention in recent years. Sustained and increased inflammation is a common feature of UAD, which is inevitably accompanied with marked gene modification and tight gene regulation. However, gene regulation in the common inflammatory processes in UAD remains unclear. MicroRNA (miRNA), a novel regulator of gene expression, has been considered to be involved in many inflammatory diseases. Although there are an increasing number of studies of miRNAs in inflammatory upper and lower airway diseases, few miRNAs have been identified that directly link the upper and lower airways. In this article, therefore, we reviewed the relevant studies available in order to improve the understanding of the roles of miRNAs in the interaction and pathogenesis of UAD. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessReview MicroRNAs Regulate Mitochondrial Function in Cerebral Ischemia-Reperfusion Injury
Int. J. Mol. Sci. 2015, 16(10), 24895-24917; doi:10.3390/ijms161024895
Received: 16 August 2015 / Revised: 25 September 2015 / Accepted: 8 October 2015 / Published: 20 October 2015
Cited by 10 | PDF Full-text (1265 KB) | HTML Full-text | XML Full-text
Abstract
Cerebral ischemia-reperfusion injury involves multiple independently fatal terminal pathways in the mitochondria. These pathways include the reactive oxygen species (ROS) generation caused by changes in mitochondrial membrane potential and calcium overload, resulting in apoptosis via cytochrome c (Cyt c) release. In addition, numerous
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Cerebral ischemia-reperfusion injury involves multiple independently fatal terminal pathways in the mitochondria. These pathways include the reactive oxygen species (ROS) generation caused by changes in mitochondrial membrane potential and calcium overload, resulting in apoptosis via cytochrome c (Cyt c) release. In addition, numerous microRNAs are associated with the overall process. In this review, we first briefly summarize the mitochondrial changes in cerebral ischemia-reperfusion and then describe the possible molecular mechanism of miRNA-regulated mitochondrial function, which likely includes oxidative stress and energy metabolism, as well as apoptosis. On the basis of the preceding analysis, we conclude that studies of microRNAs that regulate mitochondrial function will expedite the development of treatments for cerebral ischemia-reperfusion injury. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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