Special Issue "Regulation by non-coding RNAs"
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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry, Molecular Biology and Biophysics".
Deadline for manuscript submissions: closed (30 May 2013)
Special Issue Editors
Guest Editor
Prof. Dr. Nicholas Delihas
Department of Molecular Genetics and Microbiology, School of Medicine, 158 Life Sciences Building, Stony Brook University, Stony Brook, NY 11794, USA
Website: http://www.mgm.stonybrook.edu/delihas/index.shtml
E-Mail: Nicholas.delihas@stonybrook.edu
Phone: +1 631 632 8779
Fax: +1 631 632 9797
Interests: regulation of gene expression by small RNAs; annotation of genes; repetitive sequences in intergenic regions in bacteria
Co-Guest Editor
Prof. Dr. Constantinos Stathopoulos
Department of Biochemistry, School of Medicine, University of Patras, 1 Asklipiou st., 26504 Patras, Greece
Website: http://biochemistry.med.upatras.gr/lang_en/laboratory/viewCV/2
E-Mail: cstath@med.upatras.gr
Phone: +30 2610 997932 (office); +30 2610 997936 (lab)
Fax: +30 2610 969167
Special Issue Information
Dear Colleagues,
Regulatory non-protein-coding RNA genes and their transcripts were first found and characterized in bacteria but encompass all biological kingdoms. The complexity of non-coding RNAs (ncRNAs) in terms of number and types increases with degree of biological development, whereby humans and other primates appear to have the largest number. Many regulatory ncRNAs base-pair to a target RNA or DNA and inhibit target function. Bacterial ncRNA genes largely respond to environmental stress conditions and help protect the organism from adverse conditions. The prokaryotic RNAs are for the most part small (<200 bp) and are commonly referred to as small regulatory RNAs (sRNAs). Eukaryotic RNAs consist of small <200 nt RNAs and large >200 nt (termed lncRNAs). The eukaryotic small RNAs include miRNAs, siRNAs, and piRNAs. miRNAs inhibit mRNA functions and may also be associated with cancer. lncRNAs functions are multifaceted and include epigenetic regulation and animal development. The bacterial and archeal immune system CRISPR, and the eukaryotic piwi-interacting RNAs (piRNA) immune system that inhibits mobile elements in germ line cells both function by via RNA transcript/ target DNA heteroduplex base-pairing are a specific class of RNAs that protect cells from invading transposons/and or viruses. siRNAs function in plant and invertebrate immune systems and protect against viral infections. Additionally, small RNA fragments derived from snoRNAs and tRNAs as well as18 nt RNAs (tiRNAs) derived from eukaryotic transcription start sites may play a role in regulation. Exciting new findings with non-protein coding sequences of the human genome show that a major portion of the genome is transcribed. This provides the possibility that larger numbers of functional RNAs may be found in addition to the several thousand known ones. The precepts of genes and genetic inheritance may have to change to include RNA genes and their transcripts and this would represent a starling change in the principles of molecular genetics.
This special issue of IJMS will be devoted to original papers and reviews of properties and mechanism of action of regulatory non-coding RNAs and will be organized into prokaryotic and eukaryotic RNAs with separate subtopics involving regulatory ncRNAs in plants and animals. There will be a special emphasis on RNAs in humans and their significance to disease formation and will include roles of ncRNAs in neurodegeneration, cancer, diabetes and other diseases.
Prof. Dr. Nicholas Delihas
Prof. Dr. Constantinos Stathopoulos
Guest Editor
Similar Special Issues could be found in the following:
Special Issue "Non-Coding RNAs 2012"
http://www.mdpi.com/journal/ijms/special_issues/rna_2012
Special Issue "Non-Coding RNAs"
http://www.mdpi.com/journal/ijms/special_issues/noncoding_RNAs
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF.
Keywords
- Regulatory RNA
- sRNA
- ncRNA
- lncRNA
- miRNA
- siRNA
- piRNA
- CRISPR RNA
- regulatory small RNA fragments
Published Papers (10 papers)
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Received: 24 December 2012; in revised form: 23 January 2013 / Accepted: 4 February 2013 / Published: 8 February 2013
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Abstract: To better understand the molecular mechanisms of paclitaxel resistance in ovarian carcinoma, we evaluated the expression of miRNAs using miRNA microarray between human ovarian carcinoma SKOV3 cells and paclitaxel resistant SKOV3-TR30 cells. Results showed that 69 miRNAs were upregulated while 102 miRNAs were downregulated in SKOV3-TR30 cells. Using real-time PCR, we further clarified that miR-17~92 was overexpressed in SKOV3-TR30 cells compared with that in SKOV3 cells. We then established stable virally transduced SKOV3-TR30-m-PTIP-Sponge all SKOV3-TR30 cells and its vector-only control SKOV3-TR30-m-PTIP-GFP cells. Real time-PCR revealed that SKOV3-TR30-m-PTIP-Sponge all cells expressed approximately 6.18-fold lower levels of miR-17~92 compared with the control group. Decreased expression of miR-17~92 resulted in cell cycle arrest in the G2/M phase and growth inhibition. After the transduction, the BIM protein level was increased in SKOV3-TR30 cells and luciferase reporter assays revealed that miR-17~92 binds directly to the 3'-UTR of BIM. Results of luciferase reporter assays accompanied with Western Blot showed that although miR-17~92 binds directly to the 3'-UTR of PTEN, the PTEN protein expression level was upregulated slightly while the result is of no statistical significance. Our results showed that miR-17~92 could be a causal factor of the downregulation of BIM in SKOV3-TR30 cells and thus induce the paclitaxel resistance in SKOV3-TR30 cells.
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Received: 21 November 2012; in revised form: 6 January 2013 / Accepted: 7 January 2013 / Published: 21 February 2013
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Abstract: Tendon adhesions are one of the most concerning complications after surgical repair of flexor tendon injury. Extracellular signal-regulated kinase (ERK) 2 plays crucial roles in fibroblast proliferation and collagen expression which contributes to the formation of tendon adhesions after flexor tendon surgery. Using a chicken model, we have examined the effects of a small interfering RNA (siRNA) targeting ERK2 delivered by a lentiviral system on tendon adhesion formation with an adhesion scoring system, histological assessment, and biomechanical evaluation. It was found that ERK2 siRNA effectively suppressed the increase of fibroblasts and the formation of tendon adhesions (p < 0.05 compared with the control group). Moreover, no statistically significant reduction in breaking force was detected between the ERK2 siRNA group and the control group. These results show that the lentiviral-mediated siRNA system is effective in preventing tendon adhesion formation but not to tendon healing, and may be used for tendon repair after confirmation and improvement by future detailed studies.
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Received: 1 November 2012; in revised form: 3 January 2013 / Accepted: 31 January 2013 / Published: 26 February 2013
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Abstract: Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome and are emerging as new players in tumorigenesis due to their various functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. LncRNAs are deregulated in a number of cancers, demonstrating both oncogenic and tumor suppressive roles, thus suggesting their aberrant expression may be a substantial contributor in cancer development. In this review, we will summarize their emerging role in human cancer and discuss their perspectives in diagnostics as potential biomarkers.
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Received: 7 January 2013; in revised form: 1 April 2013 / Accepted: 2 April 2013 / Published: 15 April 2013
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Abstract: MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules that play important roles in a variety of normal and diseased biological processes by post-transcriptionally regulating the expression of target genes. They can bind to target messenger RNA (mRNA) transcripts of protein-coding genes and negatively control their translation or cause mRNA degradation. miRNAs have been found to actively regulate a variety of cellular processes, including cell proliferation, death, and metabolism. Therefore, their study is crucial for the better understanding of cellular functions in eukaryotes. To better understand the mechanisms of miRNA: mRNA interaction and their cellular functions, it is important to identify the miRNA targets accurately. In this paper, we provide a brief review for the advances in the animal miRNA target prediction methods and available resources to facilitate further study of miRNAs and their functions.
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Received: 20 March 2013; in revised form: 15 April 2013 / Accepted: 17 April 2013 / Published: 22 April 2013
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Abstract: Intermuscular adipose tissue is located between the muscle fiber bundles in skeletal muscles, and has similar metabolic features to visceral adipose tissue, which has been found to be related to a number of obesity-related diseases. Although various miRNAs are known to play crucial roles in adipose deposition and adipogenesis, the microRNA transcriptome of intermuscular adipose tissue has not, until now, been studied. Here, we sequenced the miRNA transcriptomes of porcine intermuscular adipose tissue by small RNA-sequencing and compared it to a representative subcutaneous adipose tissue. We found that the inflammation- and diabetes-related miRNAs were significantly enriched in the intermuscular rather than in the subcutaneous adipose tissue. A functional enrichment analysis of the genes predicted to be targeted by the enriched miRNAs also indicated that intermuscular adipose tissue was associated mainly with immune and inflammation responses. Our results suggest that the intermuscular adipose tissue should be recognized as a potential metabolic risk factor of obesity.
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Received: 27 March 2013; in revised form: 19 April 2013 / Accepted: 25 April 2013 / Published: 29 April 2013
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Abstract: Helicobacter pylori (H. pylori) infection is the main cause of gastritis, gastro-duodenal ulcer, and gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs that function as endogenous silencers of numerous target genes. Many miRNA genes are expressed in a tissue-specific manner and play important roles in cell proliferation, apoptosis, and differentiation. Recent discoveries have shed new light on the involvement of miRNAs in gastric malignancy. However, at the same time, several miRNAs have been associated with opposing events, leading to reduced inflammation, inhibition of malignancy, and increased apoptosis of transformed cells. The regulation of miRNA expression could be a novel strategy in the chemoprevention of human gastric malignancy. In this article, the biological importance of miRNAs in gastric malignancy is summarized.
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Received: 21 March 2013; in revised form: 15 April 2013 / Accepted: 6 May 2013 / Published: 27 May 2013
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Abstract: Most of the intracellular endogenous microRNAs (endo-miRNAs) are considered to be saturated in Argonaute (Ago) proteins in the RNA-induced silencing complexes (RISCs). When exogenous miRNAs (exo-miRNAs) are introduced into cells, endo-miRNAs in the RISC may be replaced with exo-miRNAs or exo-miRNAs, and endo-miRNAs might also compete for the position in the newly synthesized RISC with each other. This would lead to the fluctuation of global gene expression not only by repression of exo-miRNA target gene expression, but also by the increase of the endo-miRNA target gene expression. In the present study, we quantified the changes in the expression levels of target genes of exo-miRNA and endo-miRNA in the cells transfected with fifteen different exo-miRNAs by microarray experiments. Different exo-miRNAs increased ratios of expression levels of target genes of a given endo-miRNA to different extents, suggesting that the replacement efficiencies might differ according to the exo-miRNA types. However, the increased ratios in the expression levels of each endo-miRNA target genes by the transfection of any particular exo-miRNA were mostly equivalent, suggesting that the endo-miRNAs present in the RISC might be replaced with excessive exo-miRNAs at similar levels, probably because they exist in single-stranded forms in the RISC.
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Tilde V. Eskildsen, Pia L. Jeppesen, Mikael Schneider, Anne Y. Nossent, Maria B. Sandberg, Pernille B. L. Hansen, Charlotte H. Jensen, Maria L. Hansen, Niels Marcussen, Lars M. Rasmussen, Peter Bie, Ditte C. Andersen and Søren P. Sheikh
Received: 21 March 2013; in revised form: 25 April 2013 / Accepted: 15 May 2013 / Published: 27 May 2013
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Abstract: MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, are emerging as key regulators in cardiovascular development and disease. MiRNAs are involved in cardiac hypertrophy, heart failure and remodeling following cardiac infarction; however, miRNAs involved in hypertension have not been thoroughly investigated. We have recently reported that specific miRNAs play an integral role in Angiotensin II receptor (AT1R) signaling, especially after activation of the Gαq signaling pathway. Since AT1R blockers are widely used to treat hypertension, we undertook a detailed analysis of potential miRNAs involved in Angiotensin II (AngII) mediated hypertension in rats and hypertensive patients, using miRNA microarray and qPCR analysis. The miR-132 and miR-212 are highly increased in the heart, aortic wall and kidney of rats with hypertension (159 ± 12 mm Hg) and cardiac hypertrophy following chronic AngII infusion. In addition, activation of the endothelin receptor, another Gαq coupled receptor, also increased miR-132 and miR-212. We sought to extend these observations using human samples by reasoning that AT1R blockers may decrease miR-132 and miR-212. We analyzed tissue samples of mammary artery obtained from surplus arterial tissue after coronary bypass operations. Indeed, we found a decrease in expression levels of miR-132 and miR-212 in human arteries from bypass-operated patients treated with AT1R blockers, whereas treatment with β-blockers had no effect. Taken together, these data suggest that miR-132 and miR-212 are involved in AngII induced hypertension, providing a new perspective in hypertensive disease mechanisms.
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Received: 17 April 2013; in revised form: 21 May 2013 / Accepted: 22 May 2013 / Published: 30 May 2013
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Abstract: MicroRNAs, which are small endogenous RNA regulators, have been associated with various types of cancer. Breast cancer is a major health threat for women worldwide. Many miRNAs were reported to be associated with the progression and carcinogenesis of breast cancer. In this study, we aimed to discover novel breast cancer-related miRNAs and to elucidate their functions. First, we identified confident miRNA-target pairs by combining data from miRNA target prediction databases and expression profiles of miRNA and mRNA. Then, miRNA-regulated protein interaction networks (PINs) were constructed with confident pairs and known interaction data in the human protein reference database (HPRD). Finally, the functions of miRNA-regulated PINs were elucidated by functional enrichment analysis. From the results, we identified some previously reported breast cancer-related miRNAs and functions of the PINs, e.g., miR-125b, miR-125a, miR-21, and miR-497. Some novel miRNAs without known association to breast cancer were also found, and the putative functions of their PINs were also elucidated. These include miR-139 and miR-383. Furthermore, we validated our results by receiver operating characteristic (ROC) curve analysis using our miRNA expression profile data, gene expression-based outcome for breast cancer online (GOBO) survival analysis, and a literature search. Our results may provide new insights for research in breast cancer-associated miRNAs.
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Received: 29 March 2013; in revised form: 14 May 2013 / Accepted: 22 May 2013 / Published: 7 June 2013
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Abstract: The human polycistronic miRNA cluster miR-17-92 is frequently overexpressed in hematopoietic malignancies and cancers. Its transcription is in part controlled by an E2F-regulated host gene promoter. An intronic A/T-rich region directly upstream of the miRNA coding region also contributes to cluster expression. Our deletion analysis of the A/T-rich region revealed a strong dependence on c-Myc binding to the functional E3 site. Yet, constructs lacking the 5'-proximal ~1.3 kb or 3'-distal ~0.1 kb of the 1.5 kb A/T-rich region still retained residual specific promoter activity, suggesting multiple transcription start sites (TSS) in this region. Furthermore, the protooncogenic kinase, Pim-1, its phosphorylation target HP1γ and c-Myc colocalize to the E3 region, as inferred from chromatin immunoprecipitation. Analysis of pri-miR-17-92 expression levels in K562 and HeLa cells revealed that silencing of E2F3, c-Myc or Pim-1 negatively affects cluster expression, with a synergistic effect caused by c-Myc/Pim-1 double knockdown in HeLa cells. Thus, we show, for the first time, that the protooncogene Pim-1 is part of the network that regulates transcription of the human miR-17-92 cluster.
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Last update: 12 November 2012
