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MicroRNA in Solid Tumor and Hematological Diseases 2.0
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MicroRNA in Solid Tumor and Hematological Diseases 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 42864

Special Issue Editor

Dr. Francesca Lovat

E-Mail Website
Guest Editor
Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA
Interests: tumors; cancer research; cell biology; cancer diagnostics; cancer genetics; molecular biology; mouse model
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

MicroRNAs (miRNAs), short non-coding RNA, are involved in physiologic and pathologic processes. They are critically involved in a wide number of processes such as differentiation, development, inflammation, immune response, and cancer. MiRNAs play a key role in cancer pathogenesis by inhibiting gene expression at the post-transcriptional level. Moreover, miRNAs are differentially expressed in tumors compared to normal human tissues and they can be divided into oncomiRNAs and tumor suppressor miRNAs, although some miRNAs can act both roles depending on the cellular context. As a potential therapeutic approach for cancer, extensive studies have demonstrated how to deregulate the small non-coding transcriptome, whether down-regulating the expression of oncogenic miRNAs or overexpressing tumor-suppressive miRNAs. Therefore, the accurate analysis of miRNAs expression from cancer patients might be a useful tool to develop personalized medicine in the future.

This Special Issue will focus on the role of miRNAs in controlling pivotal biological mechanisms that lead to oncogenic transformation and tumor formation, growth, and dissemination, as well as their diagnostic and prognostic significance in different cancer subtypes. Original research manuscripts and comprehensive reviews are both welcome for this call.

Dr. Francesca Lovat
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines 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 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microRNAs
  • solid tumor
  • hematologic malignancies
  • cellular pathway analysis
  • biomarkers
  • cancer genetics
  • gene expression
  • mouse models

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Published Papers (15 papers)

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Research

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25 pages, 6063 KiB  
Article
Integration of miRNA:mRNA Co-Expression Revealed Crucial Mechanisms Modulated in Immunogenic Cancer Cell Death
by María Julia Lamberti, Barbara Montico, Maria Ravo, Annunziata Nigro, Giorgio Giurato, Roberta Iorio, Roberta Tarallo, Alessandro Weisz, Cristiana Stellato, Agostino Steffan, Riccardo Dolcetti, Vincenzo Casolaro, Damiana Antonia Faè and Jessica Dal Col
Biomedicines 2022, 10(8), 1896; https://doi.org/10.3390/biomedicines10081896 - 05 Aug 2022
Cited by 2 | Viewed by 2317
Abstract
Immunogenic cell death (ICD) in cancer represents a functionally unique therapeutic response that can induce tumor-targeting immune responses. ICD is characterized by the exposure and release of numerous damage-associated molecular patterns (DAMPs), which confer adjuvanticity to dying cancer cells. The spatiotemporally defined emission [...] Read more.
Immunogenic cell death (ICD) in cancer represents a functionally unique therapeutic response that can induce tumor-targeting immune responses. ICD is characterized by the exposure and release of numerous damage-associated molecular patterns (DAMPs), which confer adjuvanticity to dying cancer cells. The spatiotemporally defined emission of DAMPs during ICD has been well described, whereas the epigenetic mechanisms that regulate ICD hallmarks have not yet been deeply elucidated. Here, we aimed to examine the involvement of miRNAs and their putative targets using well-established in vitro models of ICD. To this end, B cell lymphoma (Mino) and breast cancer (MDA-MB-231) cell lines were exposed to two different ICD inducers, the combination of retinoic acid (RA) and interferon-alpha (IFN-α) and doxorubicin, and to non ICD inducers such as gamma irradiation. Then, miRNA and mRNA profiles were studied by next generation sequencing. Co-expression analysis identified 16 miRNAs differentially modulated in cells undergoing ICD. Integrated miRNA-mRNA functional analysis revealed candidate miRNAs, mRNAs, and modulated pathways associated with Immune System Process (GO Term). Specifically, ICD induced a distinctive transcriptional signature hallmarked by regulation of antigen presentation, a crucial step for proper activation of immune system antitumor response. Interestingly, the major histocompatibility complex class I (MHC-I) pathway was upregulated whereas class II (MHC-II) was downregulated. Analysis of MHC-II associated transcripts and HLA-DR surface expression confirmed inhibition of this pathway by ICD on lymphoma cells. miR-4284 and miR-212-3p were the strongest miRNAs upregulated by ICD associated with this event and miR-212-3p overexpression was able to downregulate surface expression of HLA-DR. It is well known that MHC-II expression on tumor cells facilitates the recruitment of CD4+ T cells. However, the interaction between tumor MHC-II and inhibitory coreceptors on tumor-associated lymphocytes could provide an immunosuppressive signal that directly represses effector cytotoxic activity. In this context, MHC-II downregulation by ICD could enhance antitumor immunity. Overall, we found that the miRNA profile was significantly altered during ICD. Several miRNAs are predicted to be involved in the regulation of MHC-I and II pathways, whose implication in ICD is demonstrated herein for the first time, which could eventually modulate tumor recognition and attack by the immune system. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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19 pages, 3474 KiB  
Article
Therapeutic miR-506-3p Replacement in Pancreatic Carcinoma Leads to Multiple Effects including Autophagy, Apoptosis, Senescence, and Mitochondrial Alterations In Vitro and In Vivo
by Hannes Borchardt, Alexander Kogel, Hermann Kalwa, Ulrike Weirauch and Achim Aigner
Biomedicines 2022, 10(7), 1692; https://doi.org/10.3390/biomedicines10071692 - 13 Jul 2022
Cited by 7 | Viewed by 1837
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality. Considering its very poor prognosis, novel treatment options are urgently needed. MicroRNAs (miRNAs) are involved in the regulation of various physiological and pathological processes. In tumors, aberrant downregulation of given miRNAs may [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality. Considering its very poor prognosis, novel treatment options are urgently needed. MicroRNAs (miRNAs) are involved in the regulation of various physiological and pathological processes. In tumors, aberrant downregulation of given miRNAs may result in pathological overexpression of oncogenes, rendering miRNA replacement as a promising therapeutic strategy. In different tumor entities, miRNA-506-3p (miR506-3p) has been ambivalently described as tumor suppressing or oncogenic. In PDAC, miR-506 is mainly considered as a tumor-suppressing miRNA. In this study, we extensively analyze the cellular and molecular effects of miRNA-506-3p replacement in different PDAC cell lines. Beyond profound antiproliferation and induction of cell death and autophagy, we describe new cellular miR506-3p effects, i.e., induction of senescence and reactive oxygen species (ROS), as well as alterations in mitochondrial potential and structure, and identify multiple underlying molecular effects. In a preclinical therapy study, PDAC xenograft-bearing mice were treated with nanoparticle-formulated miRNA-506 mimics. Profound tumor inhibition upon systemic miRNA-506 administration was associated with multiple cellular and molecular effects. This demonstrates miRNA replacement as a potential therapeutic option for PDAC patients. Due to its broad mechanisms of action on multiple relevant target genes, miR506-3p is identified as a particularly powerful tumor-inhibitory miRNA. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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19 pages, 4324 KiB  
Article
Impact of miR-1/miR-133 Clustered miRNAs: PFN2 Facilitates Malignant Phenotypes in Head and Neck Squamous Cell Carcinoma
by Shunichi Asai, Ayaka Koma, Nijiro Nohata, Takashi Kinoshita, Naoko Kikkawa, Mayuko Kato, Chikashi Minemura, Katsuhiro Uzawa, Toyoyuki Hanazawa and Naohiko Seki
Biomedicines 2022, 10(3), 663; https://doi.org/10.3390/biomedicines10030663 - 12 Mar 2022
Cited by 3 | Viewed by 2306
Abstract
Based on our original RNA sequence-based microRNA (miRNA) signatures of head and neck squamous cell carcinoma (HNSCC), it was revealed that the expression levels of miR-1-3p, miR-206, miR-133a-3p, and miR-133b were significantly suppressed in cancer specimens. Seed sequences of miR-1-3p [...] Read more.
Based on our original RNA sequence-based microRNA (miRNA) signatures of head and neck squamous cell carcinoma (HNSCC), it was revealed that the expression levels of miR-1-3p, miR-206, miR-133a-3p, and miR-133b were significantly suppressed in cancer specimens. Seed sequences of miR-1-3p/miR-206 and miR-133a-3p/miR-133b are identical. Interestingly, miR-1-3p/miR-133a-3p and miR-206/miR-133b are clustered in the human genome. We hypothesized that the genes coordinately controlled by these miRNAs are closely involved in the malignant transformation of HNSCC. Our in silico analysis identified a total of 28 genes that had putative miR-1-3p/miR-133a-3p and miR-206/miR-133b binding sites. Moreover, their expression levels were upregulated in HNSCC tissues. Multivariate Cox regression analyses showed that expression of PFN2 and PSEN1 were independent prognostic factors for patients with HNSCC (p < 0.05). Notably, four miRNAs (i.e., miR-1-3p, miR-206, miR-133a-3p, and miR-133b) directly bound the 3′untranslated region of PFN2 and controlled expression of the gene in HNSCC cells. Overexpression of PFN2 was confirmed in clinical specimens, and its aberrant expression facilitated cancer cell migration and invasion abilities. Our miRNA-based strategy continues to uncover novel genes closely involved in the oncogenesis of HNSCC. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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20 pages, 6141 KiB  
Article
Regulation of Oncogenic Targets by Tumor-Suppressive miR-150-3p in Lung Squamous Cell Carcinoma
by Keiko Mizuno, Kengo Tanigawa, Shunsuke Misono, Takayuki Suetsugu, Hiroki Sanada, Akifumi Uchida, Minami Kawano, Kentaro Machida, Shunichi Asai, Shogo Moriya, Hiromasa Inoue and Naohiko Seki
Biomedicines 2021, 9(12), 1883; https://doi.org/10.3390/biomedicines9121883 - 11 Dec 2021
Cited by 6 | Viewed by 2673
Abstract
Several recent studies have shown that both strands of certain miRNAs derived from miRNA duplexes are involved in cancer pathogenesis. Our own recent studies revealed that both strands of the miR-150 duplex act as tumor-suppressive miRNAs in lung adenocarcinoma (LUAD) through the targeting [...] Read more.
Several recent studies have shown that both strands of certain miRNAs derived from miRNA duplexes are involved in cancer pathogenesis. Our own recent studies revealed that both strands of the miR-150 duplex act as tumor-suppressive miRNAs in lung adenocarcinoma (LUAD) through the targeting of several oncogenes. The aim of the study here was to further investigate the tumor-suppressive roles of miR-150-3p (the passenger strand) in lung squamous cell carcinoma (LUSQ) and its control of cancer-promoting genes in LUSQ cells. The downregulation of miR-150-3p in LUSQ tissues was confirmed by data in The Cancer Genome Atlas (TCGA). The ectopic expression of miR-150-3p attenuated cancer cell aggressive features, e.g., cell cycle arrest, migration and invasive abilities. Our target search strategy successfully identified a total of 49 putative targets that were listed as subjects of miR-150-3p regulation in LUSQ cells. Interestingly, among these targets, 17 genes were categorized as related to the “cell cycle” based on Gene Ontology (GO) classification, namely CENPA, CIT, CCNE1, CCNE2, TIMELESS, BUB1, MCM4, HELLS, SKA3, CDCA2, FANCD2, NUF2, E2F2, SUV39H2, CASC5, ZWILCH and CKAP2). Moreover, we show that the expression of HELLS (helicase, lymphoid specific) is directly controlled by miR-150-3p, and its expression promotes the malignant phenotype of LUSQ cells. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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15 pages, 2936 KiB  
Article
miRNA-148a Enhances the Treatment Response of Patients with Rectal Cancer to Chemoradiation and Promotes Apoptosis by Directly Targeting c-Met
by Chun-Ming Huang, Ming-Yii Huang, Yen-Cheng Chen, Po-Jung Chen, Wei-Chih Su, Tsung-Kun Chang, Ching-Chun Li, Ching-Wen Huang, Hsiang-Lin Tsai and Jaw-Yuan Wang
Biomedicines 2021, 9(10), 1371; https://doi.org/10.3390/biomedicines9101371 - 01 Oct 2021
Cited by 9 | Viewed by 1821
Abstract
Patients with locally advanced rectal cancer (LARC) who achieve a pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NACRT) have an excellent prognosis, but only approximately 30% of patients achieve pCR. Therefore, identifying predictors of pCR is imperative. We employed a microRNA (miRNA) microarray [...] Read more.
Patients with locally advanced rectal cancer (LARC) who achieve a pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NACRT) have an excellent prognosis, but only approximately 30% of patients achieve pCR. Therefore, identifying predictors of pCR is imperative. We employed a microRNA (miRNA) microarray to compare the miRNA profiles of patients with LARC who achieved pCR (pCR group, n = 5) with those who did not (non-pCR group, n = 5). The validation set confirmed that miRNA-148a was overexpressed in the pCR group (n = 11) compared with the non-pCR group (n = 40). Cell proliferation and clonogenic assays revealed that miRNA-148a overexpression radio-sensitized cancer cells and inhibited cellular proliferation, before and after irradiation (p < 0.01). Apoptosis assays demonstrated that miRNA-148a enhanced apoptosis before and after irradiation. Reporter assays revealed that c-Met was the direct target gene of miRNA-148a. An in vivo study indicated that miRNA-148a enhanced the irradiation-induced suppression of xenograft tumor growth (p < 0.01). miRNA-148a may be a biomarker of pCR following NACRT and can promote apoptosis and inhibit proliferation in CRC cells by directly targeting c-Met in vitro and enhancing tumor response to irradiation in vivo. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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16 pages, 4081 KiB  
Article
Pan-Cancer Analysis Reveals Common and Specific Relationships between Intragenic miRNAs and Their Host Genes
by Baohong Liu, Yu Shyr and Qi Liu
Biomedicines 2021, 9(9), 1263; https://doi.org/10.3390/biomedicines9091263 - 18 Sep 2021
Cited by 2 | Viewed by 1944
Abstract
MicroRNAs (miRNAs) are small endogenous non-coding RNAs that play important roles in regulating gene expression. Most miRNAs are located within or close to genes (host). miRNAs and their host genes have either coordinated or independent transcription. We performed a comprehensive investigation on co-transcriptional [...] Read more.
MicroRNAs (miRNAs) are small endogenous non-coding RNAs that play important roles in regulating gene expression. Most miRNAs are located within or close to genes (host). miRNAs and their host genes have either coordinated or independent transcription. We performed a comprehensive investigation on co-transcriptional patterns of miRNAs and host genes based on 4707 patients across 21 cancer types. We found that only 11.6% of miRNA-host pairs were co-transcribed consistently and strongly across cancer types. Most miRNA-host pairs showed a strong coexpression only in some specific cancer types, demonstrating a high heterogenous pattern. For two particular types of intergenic miRNAs, readthrough and divergent miRNAs, readthrough miRNAs showed higher coexpression with their host genes than divergent ones. miRNAs located within non-coding genes had tighter co-transcription with their hosts than those located within protein-coding genes, especially exonic and junction miRNAs. A few precursor miRNAs changed their dominate form between 5′ and 3′ strands in different cancer types, including miR-486, miR-99b, let-7e, miR-125a, let-7g, miR-339, miR-26a, miR-16, and miR-218, whereas only two miRNAs with multiple host genes switched their co-transcriptional partner in different cancer types (miR-219a-1 with SLC39A7/HSD17B8 and miR-3615 with RAB37/SLC9A3R1). miRNAs generated from distinct precursors (such as miR-125b from miR-125b-1 or miR-125b-2) were more likely to have cancer-dependent main contributors. miRNAs and hosts were less co-expressed in KIRC than other cancer types, possibly due to its frequent VHL mutations. Our findings shed new light on miRNA biogenesis and cancer diagnosis and treatments. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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14 pages, 421 KiB  
Article
Heterogeneous Types of miRNA-Disease Associations Stratified by Multi-Layer Network Embedding and Prediction
by Dong-Ling Yu, Zu-Guo Yu, Guo-Sheng Han, Jinyan Li and Vo Anh
Biomedicines 2021, 9(9), 1152; https://doi.org/10.3390/biomedicines9091152 - 03 Sep 2021
Cited by 5 | Viewed by 1881
Abstract
Abnormal miRNA functions are widely involved in many diseases recorded in the database of experimentally supported human miRNA-disease associations (HMDD). Some of the associations are complicated: There can be up to five heterogeneous association types of miRNA with the same disease, including genetics [...] Read more.
Abnormal miRNA functions are widely involved in many diseases recorded in the database of experimentally supported human miRNA-disease associations (HMDD). Some of the associations are complicated: There can be up to five heterogeneous association types of miRNA with the same disease, including genetics type, epigenetics type, circulating miRNAs type, miRNA tissue expression type and miRNA-target interaction type. When one type of association is known for an miRNA-disease pair, it is important to predict any other types of the association for a better understanding of the disease mechanism. It is even more important to reveal associations for currently unassociated miRNAs and diseases. Methods have been recently proposed to make predictions on the association types of miRNA-disease pairs through restricted Boltzman machines, label propagation theories and tensor completion algorithms. None of them has exploited the non-linear characteristics in the miRNA-disease association network to improve the performance. We propose to use attributed multi-layer heterogeneous network embedding to learn the latent representations of miRNAs and diseases from each association type and then to predict the existence of the association type for all the miRNA-disease pairs. The performance of our method is compared with two newest methods via 10-fold cross-validation on the database HMDD v3.2 to demonstrate the superior prediction achieved by our method under different settings. Moreover, our real predictions made beyond the HMDD database can be all validated by NCBI literatures, confirming that our method is capable of accurately predicting new associations of miRNAs with diseases and their association types as well. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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10 pages, 2010 KiB  
Article
MicroRNA-138 Increases Chemo-Sensitivity of Glioblastoma through Downregulation of Survivin
by Ji-Young Yoo, Margaret Yeh, Yin-Ying Wang, Christina Oh, Zhong-Ming Zhao, Balveen Kaur and Tae-Jin Lee
Biomedicines 2021, 9(7), 780; https://doi.org/10.3390/biomedicines9070780 - 06 Jul 2021
Cited by 5 | Viewed by 2097
Abstract
Glioblastoma (GBM) is one of the most deadly cancers and poorly responses to chemotherapies, such as temozolomide (TMZ). Dysregulation of intrinsic signaling pathways in cancer cells are often resulted by dysregulated tumor suppressive microRNAs (miRNAs). Previously, we found miR-138 as one of tumor [...] Read more.
Glioblastoma (GBM) is one of the most deadly cancers and poorly responses to chemotherapies, such as temozolomide (TMZ). Dysregulation of intrinsic signaling pathways in cancer cells are often resulted by dysregulated tumor suppressive microRNAs (miRNAs). Previously, we found miR-138 as one of tumor suppressive miRNAs that were significantly down-regulated in GBM. In this study, we demonstrated that ectopic over-expression of miR-138 sensitizes GBM cells to the treatment of TMZ and increased apoptotic cell death. Mechanistically, miR-138 directly repressed the expression of Survivin, an anti-apoptotic protein, to enhance caspase-induced apoptosis upon TMZ treatment. Using an intracranial GBM xenograft mice model, we also showed that combination of miR-138 with TMZ increases survival rates of the mice compared to the control mice treated with TMZ alone. This study provides strong preclinical evidence of the therapeutic benefit from restoration of miR-138 to sensitize the GBM tumor to conventional chemotherapy. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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17 pages, 2202 KiB  
Article
Identification of MicroRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer
by Luis Javier Martínez-González, Victor Sánchez-Conde, Jose María González-Cabezuelo, Alba Antunez-Rodríguez, Eduardo Andrés-León, Inmaculada Robles-Fernandez, Jose Antonio Lorente, Fernando Vázquez-Alonso and María Jesus Alvarez-Cubero
Biomedicines 2021, 9(6), 646; https://doi.org/10.3390/biomedicines9060646 - 05 Jun 2021
Cited by 11 | Viewed by 3793
Abstract
MiRNAs play a relevant role in PC (prostate cancer) by the regulation in the expression of several pathways’ AR (androgen receptor), cellular cycle, apoptosis, MET (mesenchymal epithelium transition), or metastasis. Here, we report the role of several miRNAs’ expression patterns, such as miR-93-5p, [...] Read more.
MiRNAs play a relevant role in PC (prostate cancer) by the regulation in the expression of several pathways’ AR (androgen receptor), cellular cycle, apoptosis, MET (mesenchymal epithelium transition), or metastasis. Here, we report the role of several miRNAs’ expression patterns, such as miR-93-5p, miR-23c, miR-210-3p, miR-221-3p, miR-592, miR-141, miR-375, and miR-130b, with relevance in processes like cell proliferation and MET. Using Trizol® extraction protocol and TaqMan™ specific probes for amplification, we performed miRNAs’ analysis of 159 PC fresh tissues and 60 plasmas from peripheral blood samples. We had clinical data from all samples including PSA, Gleason, TNM, and D’Amico risk. Moreover, a bioinformatic analysis in TCGA (The Cancer Genome Atlas) was included to analyze the effect of the most relevant miRNAs according to aggressiveness in an extensive cohort (n = 531). We found that miR-210-3p, miR-23c, miR-592, and miR-93-5p are the most suitable biomarkers for PC aggressiveness and diagnosis, respectively. In fact, according with our results, miR-93-5p seems the most promising non-invasive biomarker for PC. To sum up, miR-210-3p, miR-23c, miR-592, and miR-93-5p miRNAs are suggested to be potential biomarkers for PC risk stratification that could be included in non-invasive strategies such as liquid biopsy in precision medicine for PC management. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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Review

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27 pages, 2980 KiB  
Review
Elucidating miRNA Function in Cancer Biology via the Molecular Genetics’ Toolbox
by Adam Azlan, Yaashini Rajasegaran, Khor Kang Zi, Aliaa Arina Rosli, Mot Yee Yik, Narazah Mohd Yusoff, Olaf Heidenreich and Emmanuel Jairaj Moses
Biomedicines 2022, 10(4), 915; https://doi.org/10.3390/biomedicines10040915 - 15 Apr 2022
Cited by 4 | Viewed by 2358
Abstract
Micro-RNA (miRNAs) are short non-coding RNAs of about 18–20 nucleotides in length and are implicated in many cellular processes including proliferation, development, differentiation, apoptosis and cell signaling. Furthermore, it is well known that miRNA expression is frequently dysregulated in many cancers. Therefore, this [...] Read more.
Micro-RNA (miRNAs) are short non-coding RNAs of about 18–20 nucleotides in length and are implicated in many cellular processes including proliferation, development, differentiation, apoptosis and cell signaling. Furthermore, it is well known that miRNA expression is frequently dysregulated in many cancers. Therefore, this review will highlight the various mechanisms by which microRNAs are dysregulated in cancer. Further highlights include the abundance of molecular genetics tools that are currently available to study miRNA function as well as their advantages and disadvantages with a special focus on various CRISPR/Cas systems This review provides general workflows and some practical considerations when studying miRNA function thus enabling researchers to make informed decisions in regards to the appropriate molecular genetics tool to be utilized for their experiments. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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14 pages, 744 KiB  
Review
Breast Cancer Subtype-Specific miRNAs: Networks, Impacts, and the Potential for Intervention
by Raj Pranap Arun, Hannah F. Cahill and Paola Marcato
Biomedicines 2022, 10(3), 651; https://doi.org/10.3390/biomedicines10030651 - 11 Mar 2022
Cited by 11 | Viewed by 5239
Abstract
The regulatory and functional roles of non-coding RNAs are increasingly demonstrated as critical in cancer. Among non-coding RNAs, microRNAs (miRNAs) are the most well-studied with direct regulation of biological signals through post-transcriptional repression of mRNAs. Like the transcriptome, which varies between tissue type [...] Read more.
The regulatory and functional roles of non-coding RNAs are increasingly demonstrated as critical in cancer. Among non-coding RNAs, microRNAs (miRNAs) are the most well-studied with direct regulation of biological signals through post-transcriptional repression of mRNAs. Like the transcriptome, which varies between tissue type and disease condition, the miRNA landscape is also similarly altered and shows disease-specific changes. The importance of individual tumor-promoting or suppressing miRNAs is well documented in breast cancer; however, the implications of miRNA networks is less defined. Some evidence suggests that breast cancer subtype-specific cellular effects are influenced by distinct miRNAs and a comprehensive network of subtype-specific miRNAs and mRNAs would allow us to better understand breast cancer signaling. In this review, we discuss the altered miRNA landscape in the context of breast cancer and propose that breast cancer subtypes have distinct miRNA dysregulation. Further, given that miRNAs can be used as diagnostic and/or prognostic biomarkers, their impact as novel targets for subtype-specific therapy is also possible and suggest important implications for subtype-specific miRNAs. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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24 pages, 1261 KiB  
Review
Competitive Endogenous RNA Network Involving miRNA and lncRNA in Non-Hodgkin Lymphoma: Current Advances and Clinical Perspectives
by Mara Fernandes, Herlander Marques, Ana Luísa Teixeira and Rui Medeiros
Biomedicines 2021, 9(12), 1934; https://doi.org/10.3390/biomedicines9121934 - 17 Dec 2021
Cited by 1 | Viewed by 2695
Abstract
Non-Hodgkin lymphoma (NHL) is a heterogeneous malignancy with variable patient outcomes. There is still a lack of understanding about the different players involved in lymphomagenesis, and the identification of new diagnostic and prognostic biomarkers is urgent. MicroRNAs and long non-coding RNAs emerged as [...] Read more.
Non-Hodgkin lymphoma (NHL) is a heterogeneous malignancy with variable patient outcomes. There is still a lack of understanding about the different players involved in lymphomagenesis, and the identification of new diagnostic and prognostic biomarkers is urgent. MicroRNAs and long non-coding RNAs emerged as master regulators of B-cell development, and their deregulation has been associated with the initiation and progression of lymphomagenesis. They can function by acting alone or, as recently proposed, by creating competing endogenous RNA (ceRNA) networks. Most studies have focused on individual miRNAs/lncRNAs function in lymphoma, and there is still limited data regarding their interactions in lymphoma progression. The study of miRNAs’ and lncRNAs’ deregulation in NHL, either alone or as ceRNAs networks, offers new insights into the molecular mechanisms underlying lymphoma pathogenesis and opens a window of opportunity to identify potential diagnostic and prognostic biomarkers. In this review, we summarized the current knowledge regarding the role of miRNAs and lncRNAs in B-cell lymphoma, including their interactions and regulatory networks. Finally, we summarized the studies investigating the potential of miRNAs and lncRNAs as clinical biomarkers, with a special focus on the circulating profiles, to be applied as a non-invasive, easy-to-obtain, and reproducible liquid biopsy for dynamic management of NHL patients. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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42 pages, 4982 KiB  
Review
Footprints of microRNAs in Cancer Biology
by Yaashini Rajasegaran, Adam Azlan, Aliaa Arina Rosli, Mot Yee Yik, Khor Kang Zi, Narazah Mohd Yusoff and Emmanuel Jairaj Moses
Biomedicines 2021, 9(10), 1494; https://doi.org/10.3390/biomedicines9101494 - 19 Oct 2021
Cited by 9 | Viewed by 3247
Abstract
MicroRNAs (miRNAs) are short non-coding RNAs involved in post-transcriptional gene regulation. Over the past years, various studies have demonstrated the role of aberrant miRNA expression in the onset of cancer. The mechanisms by which miRNA exerts its cancer-promoting or inhibitory effects are apparent [...] Read more.
MicroRNAs (miRNAs) are short non-coding RNAs involved in post-transcriptional gene regulation. Over the past years, various studies have demonstrated the role of aberrant miRNA expression in the onset of cancer. The mechanisms by which miRNA exerts its cancer-promoting or inhibitory effects are apparent through the various cancer hallmarks, which include selective proliferative advantage, altered stress response, vascularization, invasion and metastasis, metabolic rewiring, the tumor microenvironment and immune modulation; therefore, this review aims to highlight the association between miRNAs and the various cancer hallmarks by dissecting the mechanisms of miRNA regulation in each hallmark separately. It is hoped that the information presented herein will provide further insights regarding the role of cancer and serve as a guideline to evaluate the potential of microRNAs to be utilized as biomarkers and therapeutic targets on a larger scale in cancer research. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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21 pages, 2902 KiB  
Review
Splice and Dice: Intronic microRNAs, Splicing and Cancer
by Alex C. H. Wong and John E. J. Rasko
Biomedicines 2021, 9(9), 1268; https://doi.org/10.3390/biomedicines9091268 - 19 Sep 2021
Cited by 8 | Viewed by 3653
Abstract
Introns span only a quarter of the human genome, yet they host around 60% of all known microRNAs. Emerging evidence indicates the adaptive advantage of microRNAs residing within introns is attributed to their complex co-regulation with transcription and alternative splicing of their host [...] Read more.
Introns span only a quarter of the human genome, yet they host around 60% of all known microRNAs. Emerging evidence indicates the adaptive advantage of microRNAs residing within introns is attributed to their complex co-regulation with transcription and alternative splicing of their host genes. Intronic microRNAs are often co-expressed with their host genes, thereby providing functional synergism or antagonism that is exploited or decoupled in cancer. Additionally, intronic microRNA biogenesis and the alternative splicing of host transcript are co-regulated and intertwined. The importance of intronic microRNAs is under-recognized in relation to the pathogenesis of cancer. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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Review
Emerging Evidence of the Functional Impact of the miR379/miR656 Cluster (C14MC) in Breast Cancer
by Elan C. McCarthy and Róisín M. Dwyer
Biomedicines 2021, 9(7), 827; https://doi.org/10.3390/biomedicines9070827 - 16 Jul 2021
Cited by 4 | Viewed by 2855
Abstract
Many microRNAs exist in clusters that share comparable sequence homology and may target genes in a common pathway. The miR-379/miR-656 (C14MC) cluster is imprinted in the DLK1-Dio3 region of 14q32.3 and contains 42 miRNAs. It plays a functional role in numerous biological pathways [...] Read more.
Many microRNAs exist in clusters that share comparable sequence homology and may target genes in a common pathway. The miR-379/miR-656 (C14MC) cluster is imprinted in the DLK1-Dio3 region of 14q32.3 and contains 42 miRNAs. It plays a functional role in numerous biological pathways including vascular remodeling and early development. With many C14MC miRNAs highlighted as potential tumor suppressors in a variety of cancers, the role of this cluster in breast cancer (BC) has garnered increased attention in recent years. This review focuses on C14MC in BC, providing an overview of the constituent miRNAs and addressing each in terms of functional impact, potential target genes/pathways, and, where relevant, biomarker capacity. Studies have revealed the regulation of key factors in disease progression and metastasis including tyrosine kinase pathways and factors critical to epithelial–mesenchymal transition (EMT). This has potentially important clinical implications, with EMT playing a critical role in BC metastasis and tyrosine kinase inhibitors (TKIs) in widespread use for the treatment of BC. While the majority of studies have reported tumor-suppressing roles for these miRNAs, some have highlighted their potential as oncomiRs. Understanding the collective contribution of miRNAs within C14MC to BC may support improved understanding of disease etiology and present novel approaches to targeted therapy. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases 2.0)
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