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New Regulators and Modulators of MicroRNA 2022
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New Regulators and Modulators of MicroRNA 2022

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 15418

Special Issue Editor

Prof. Dr. Nalini Santanam

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
Interests: oxidative stress; cardiovascular disease; obesity; microRNA; biomarker; translational research; endometriosis; ovarian cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Understanding of the role of microRNAs in the biological and clinical worlds has advanced tremendously in the past decade, with a much better understanding of their biogenesis, regulation, and function. The current research has advanced beyond simply measuring the differential expression of microRNAs in diseased versus normal conditions onto the development of methods to manipulate microRNAs for use as diagnostic and prognostic tools. New areas of research are highlighting conditions where there is crosstalk between microRNAs and other epigenetic pathways, such as DNA methylation or histone modifications. With the current interest in microbiomes, there are also suggestions of gut microbes regulating microRNAs or, in turn, being regulated by microRNAs. Exciting new findings have been made in the research field of microRNAs and, hence, we decided to revisit this topic with our Special Issue that focuses on “New Regulators and Modulators of MicroRNA”.

We invite authors to submit both original research and review articles that explore the role of new regulators and modulators of miRNAs. Potential topics include, but are not limited to, the following:

  1. MicroRNAs as disease markers—the latest advances
  2. MicroRNA regulation and editing
  3. MicroRNA regulation of other epigenetic pathways
  4. MicroRNAs in aging
  5. MicroRNAs and gut microbiomes
  6. MicroRNA and redox stress

Prof. Dr. Nalini Santanam
Guest Editor

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • microRNA biogenesis
  • microRNA editing
  • microRNA and DNA methylation
  • microRNA and histone modifications
  • microRNA and redox stress
  • microRNA and microbiomes

Published Papers (7 papers)

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Research

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20 pages, 23737 KiB  
Article
Small ORFs as New Regulators of Pri-miRNAs and miRNAs Expression in Human and Drosophila
by Christine Dozier, Audrey Montigny, Mireia Viladrich, Raphael Culerrier, Jean-Philippe Combier, Arnaud Besson and Serge Plaza
Int. J. Mol. Sci. 2022, 23(10), 5764; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105764 - 20 May 2022
Cited by 5 | Viewed by 2105
Abstract
MicroRNAs (miRNAs) are small regulatory non-coding RNAs, resulting from the cleavage of long primary transcripts (pri-miRNAs) in the nucleus by the Microprocessor complex generating precursors (pre-miRNAs) that are then exported to the cytoplasm and processed into mature miRNAs. Some miRNAs are hosted in [...] Read more.
MicroRNAs (miRNAs) are small regulatory non-coding RNAs, resulting from the cleavage of long primary transcripts (pri-miRNAs) in the nucleus by the Microprocessor complex generating precursors (pre-miRNAs) that are then exported to the cytoplasm and processed into mature miRNAs. Some miRNAs are hosted in pri-miRNAs annotated as long non-coding RNAs (lncRNAs) and defined as MIRHGs (for miRNA Host Genes). However, several lnc pri-miRNAs contain translatable small open reading frames (smORFs). If smORFs present within lncRNAs can encode functional small peptides, they can also constitute cis-regulatory elements involved in lncRNA decay. Here, we investigated the possible involvement of smORFs in the regulation of lnc pri-miRNAs in Human and Drosophila, focusing on pri-miRNAs previously shown to contain translatable smORFs. We show that smORFs regulate the expression levels of human pri-miR-155 and pri-miR-497, and Drosophila pri-miR-8 and pri-miR-14, and also affect the expression and activity of their associated miRNAs. This smORF-dependent regulation is independent of the nucleotidic and amino acidic sequences of the smORFs and is sensitive to the ribosome-stalling drug cycloheximide, suggesting the involvement of translational events. This study identifies smORFs as new cis-acting elements involved in the regulation of pri-miRNAs and miRNAs expression, in both Human and Drosophila melanogaster. Full article
(This article belongs to the Special Issue New Regulators and Modulators of MicroRNA 2022)
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17 pages, 2893 KiB  
Article
Profiling of Non-Coding Regulators and Their Targets in Epicardial Fat from Patients with Coronary Artery Disease
by Brendin Flinn, Christopher Adams, Nepal Chowdhury, Todd Gress and Nalini Santanam
Int. J. Mol. Sci. 2022, 23(10), 5297; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105297 - 10 May 2022
Cited by 5 | Viewed by 1922
Abstract
Epicardial fat is a continuously growing target of investigation in cardiovascular diseases due to both its anatomical proximity to the heart and coronary circulation and its unique physiology among adipose depots. Previous reports have demonstrated that epicardial fat plays key roles in coronary [...] Read more.
Epicardial fat is a continuously growing target of investigation in cardiovascular diseases due to both its anatomical proximity to the heart and coronary circulation and its unique physiology among adipose depots. Previous reports have demonstrated that epicardial fat plays key roles in coronary artery disease, but the non-coding RNA and transcriptomic alterations of epicardial fat in coronary artery disease have not been investigated thoroughly. Micro- and lncRNA microarrays followed by GO-KEGG functional enrichment analysis demonstrated sex-dependent unique mi/lncRNAs altered in human epicardial fat in comparison to subcutaneous fat in both patients with and without coronary artery disease (IRB approved). Among the 14 differentially expressed microRNAs in epicardial fat between patients with and without coronary artery disease, the hsa-miR-320 family was the most highly represented. IPW lncRNA interacted with three of these differentially expressed miRNAs. Next-generation sequencing and pathway enrichment analysis identified six unique mRNAs–miRNA pairs. Pathway enrichment identified inflammation, adipogenesis, and cardiomyocyte apoptosis as the most represented functions altered by the mi/lncRNAs and atherosclerosis and myocardial infarction among the highest cardiovascular pathologies associated with them. Overall, the epicardial fat in patients with coronary artery disease has a unique mi/lncRNA profile which is sex-dependent and has potential implications for regulating cardiac function. Full article
(This article belongs to the Special Issue New Regulators and Modulators of MicroRNA 2022)
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16 pages, 2855 KiB  
Article
Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3
by Myung Chan Park, Hyoji Kim, Hoyun Choi, Mee Soo Chang and Suk Kyeong Lee
Int. J. Mol. Sci. 2021, 22(20), 10936; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222010936 - 10 Oct 2021
Cited by 8 | Viewed by 1995
Abstract
Epstein-Barr virus (EBV) is associated with several tumors and generates BamHI A rightward transcript (BART) microRNAs (miRNAs) from BART transcript introns. These BART miRNAs are expressed at higher levels in EBV-associated epithelial malignancies than in EBV-infected B lymphomas. To test the effects of [...] Read more.
Epstein-Barr virus (EBV) is associated with several tumors and generates BamHI A rightward transcript (BART) microRNAs (miRNAs) from BART transcript introns. These BART miRNAs are expressed at higher levels in EBV-associated epithelial malignancies than in EBV-infected B lymphomas. To test the effects of EBV miRNA on the cell cycle and cell growth, we transfected miR-BART1-3p, a highly expressed EBV-associated miRNA, into gastric carcinoma cells. We found that miR-BART1-3p induced G0/G1 arrest and suppressed cell growth in gastric carcinoma cells. As our microarray analyses showed that E2F3, a cell cycle regulator, was inhibited by EBV infection, we hypothesized that miR-BART1-3p regulates E2F3. Luciferase assays revealed that miR-BART1-3p directly targeted the 3′-UTR of E2F3 mRNA. Both E2F3 mRNA and encoded protein levels were reduced following miR-BART1-3p transfection. In contrast, E2F3 expression in AGS-EBV cells transfected with a miR-BART1-3p inhibitor was enhanced. As E2F3 has been shown to regulate the expression of highly conserved miR-17-92 clusters in vertebrates, we examined whether this expression is affected by miR-BART1-3p, which can downregulate E2F3. The expression of E2F3, miR-17-92a-1 cluster host gene (MIR17HG), and miR-17-92 cluster miRNAs was significantly reduced in EBV-associated gastric carcinoma (EBVaGC) patients compared with EBV-negative gastric carcinoma (EBVnGC) patients. Further, miR-BART1-3p as well as the siRNA specific to E2F3 inhibited the expression of the miR-17-92 cluster, while inhibition of miR-BART1-3p enhanced the expression of the miR-17-92 cluster in cultured GC cells. Our results suggest a possible role of miR-BART1-3p in cell cycle regulation and in regulation of the miR-17-92 cluster through E2F3 suppression. Full article
(This article belongs to the Special Issue New Regulators and Modulators of MicroRNA 2022)
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16 pages, 4593 KiB  
Article
Alteration of Pituitary Tumor Transforming Gene 1 by MicroRNA-186 and 655 Regulates Invasion Ability of Human Oral Squamous Cell Carcinoma
by Sang Shin Lee, Jong Ho Choi, Seung Mook Lim, Gi Jin Kim, Suk Keun Lee and Yoon Kyung Jeon
Int. J. Mol. Sci. 2021, 22(3), 1021; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031021 - 20 Jan 2021
Cited by 5 | Viewed by 1769
Abstract
Background: Pituitary tumor-transforming gene 1 (PTTG1) was recently shown to be involved in the progression as well as the metastasis of cancers. However, their expression and function in the invasion of oral squamous cell carcinoma (SCC) remain unclear. Methods: The expressions of PTTG1 [...] Read more.
Background: Pituitary tumor-transforming gene 1 (PTTG1) was recently shown to be involved in the progression as well as the metastasis of cancers. However, their expression and function in the invasion of oral squamous cell carcinoma (SCC) remain unclear. Methods: The expressions of PTTG1 and PTTG1-targeted miRNA in oral SCC cell lines and their invasion capability depended on PTTG1 expression were analyzed by quantitative RT-PCR, Western blots, the transwell insert system and Zymography. Results: Invasion abilities were decreased in oral SCC cells treated with siRNA-PTTG1. When PTTG1 were downregulated in oral SCC cells treated with microRNA-186 and -655 inhibited their invasion abilities via MMP-9 activity. Conclusions: These results indicate that alteration of expression of PTTG1 in oral SCC cells by newly identified microRNA-186 and -655 can regulate invasion activity. Therefore, these data offer new insights into further understanding PTTG1 function in oral SCC and should provide new strategies for diagnostic markers for oral SCC. Full article
(This article belongs to the Special Issue New Regulators and Modulators of MicroRNA 2022)
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Review

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15 pages, 291 KiB  
Review
Are Non-Coding RNAs Useful Biomarkers in Parathyroid Tumorigenesis?
by Cinzia Aurilia, Simone Donati, Gaia Palmini, Francesca Miglietta, Irene Falsetti, Teresa Iantomasi and Maria Luisa Brandi
Int. J. Mol. Sci. 2021, 22(19), 10465; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910465 - 28 Sep 2021
Cited by 6 | Viewed by 1847
Abstract
Tumors of the parathyroid glands are common endocrine diseases almost always characterized by parathyroid hormone hypersecretion that determines the clinical manifestations of primary hyperparathyroidism, such as fatigue, kidney problems, weakness, brittle bones, and other symptoms. Most parathyroid neoplasia are benign adenomas, although rare [...] Read more.
Tumors of the parathyroid glands are common endocrine diseases almost always characterized by parathyroid hormone hypersecretion that determines the clinical manifestations of primary hyperparathyroidism, such as fatigue, kidney problems, weakness, brittle bones, and other symptoms. Most parathyroid neoplasia are benign adenomas, although rare malignant forms have been described. They are heterogeneous in terms of clinical presentation and the associated signs and symptoms overlap with those of disease and aging. Furthermore, most patients with hypercalcemia are discovered during routine blood tests for other reasons. Surgical removal is considered the main therapeutic option to cure these endocrine tumors and, therefore, innovative therapeutic approaches are actively required. Recently, a growing number of studies have suggested that alterations to the epigenetic mechanisms could play a pivotal role in parathyroid tumorigenesis. Most of the attention has been focused on non-coding RNAs (ncRNAs) (i.e., miRNAs, lncRNAs, and circRNAs) whose expression profile has been found to be deregulated in parathyroid tumors. The aim of the present paper is to give an insight into the ncRNAs involved in parathyroid tumorigenesis, which could be used in the future either as innovative diagnostic biomarkers or as therapeutic targets for the treatment of this endocrine neoplasia. Full article
(This article belongs to the Special Issue New Regulators and Modulators of MicroRNA 2022)
12 pages, 1299 KiB  
Review
Regulatory Role of microRNAs Targeting the Transcription Co-Factor ZNF521 in Normal Tissues and Cancers
by Emanuela Chiarella, Annamaria Aloisio, Stefania Scicchitano, Heather Mandy Bond and Maria Mesuraca
Int. J. Mol. Sci. 2021, 22(16), 8461; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168461 - 06 Aug 2021
Cited by 12 | Viewed by 2466
Abstract
Powerful bioinformatics tools have provided a wealth of novel miRNA–transcription factor networks crucial in controlling gene regulation. In this review, we focus on the biological functions of miRNAs targeting ZNF521, explaining the molecular mechanisms by which the dysregulation of this axis contributes to [...] Read more.
Powerful bioinformatics tools have provided a wealth of novel miRNA–transcription factor networks crucial in controlling gene regulation. In this review, we focus on the biological functions of miRNAs targeting ZNF521, explaining the molecular mechanisms by which the dysregulation of this axis contributes to malignancy. ZNF521 is a stem cell-associated co-transcription factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells. The aberrant expression of ZNF521 transcripts, frequently associated with miRNA deregulation, has been detected in several tumors including pancreatic, hepatocellular, gastric, bladder transitional cell carcinomas as well as in breast and ovarian cancers. miRNA expression profiling tools are currently identifying a multitude of miRNAs, involved together with oncogenes and TFs in the regulation of oncogenesis, including ZNF521, which may be candidates for diagnostic and prognostic biomarkers of cancer. Full article
(This article belongs to the Special Issue New Regulators and Modulators of MicroRNA 2022)
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16 pages, 1011 KiB  
Review
GPER1 and microRNA: Two Players in Breast Cancer Progression
by Adele Vivacqua
Int. J. Mol. Sci. 2021, 22(1), 98; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010098 - 24 Dec 2020
Cited by 6 | Viewed by 2511
Abstract
Breast cancer is the main cause of morbidity and mortality in women worldwide. However, the molecular pathogenesis of breast cancer remains poorly defined due to its heterogeneity. Several studies have reported that G Protein-Coupled Estrogen Receptor 1 (GPER1) plays a crucial role in [...] Read more.
Breast cancer is the main cause of morbidity and mortality in women worldwide. However, the molecular pathogenesis of breast cancer remains poorly defined due to its heterogeneity. Several studies have reported that G Protein-Coupled Estrogen Receptor 1 (GPER1) plays a crucial role in breast cancer progression, by binding to estrogens or synthetic agonists, like G-1, thus modulating genes involved in diverse biological events, such as cell proliferation, migration, apoptosis, and metastasis. In addition, it has been established that the dysregulation of short sequences of non-coding RNA, named microRNAs (miRNAs), is involved in various pathophysiological conditions, including breast cancer. Recent evidence has indicated that estrogens may regulate miRNA expression and therefore modulate the levels of their target genes, not only through the classical estrogen receptors (ERs), but also activating GPER1 signalling, hence suggesting an alternative molecular pathway involved in breast tumor progression. Here, the current knowledge about GPER1 and miRNA action in breast cancer is recapitulated, reporting recent evidence on the liaison of these two players in triggering breast tumorogenic effects. Elucidating the role of GPER1 and miRNAs in breast cancer might provide new tools for innovative approaches in anti-cancer therapy. Full article
(This article belongs to the Special Issue New Regulators and Modulators of MicroRNA 2022)
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