Topic Editors

Department of Physics, Chuo University, Tokyo 112-8551, Japan
Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan

MicroRNA: Mechanisms of Action, Physio-Pathological Implications, and Disease Biomarkers, 2nd Volume

Abstract submission deadline
20 February 2024
Manuscript submission deadline
20 April 2024
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Topic Information

Dear Colleagues,

MicroRNAs (miRNAs) are known to be one of the most widespread non-coding RNAs, contributing to a wide range of biological processes, including disease development. Thus, it is critically important to understand the mechanisms by which various miRNAs mediate the post-transcriptional regulation of gene expression. miRNA functions have been extensively investigated in experiments and clinical studies. The exploration of miRNA disease or diagnosis biomarkers has become a popular research topic in recent years. In addition to investigating miRNA biomarkers and miRNA mechanisms, miRNA-based therapeutics such as treatment-targeting miRNAs or miRNA drug discovery present potentially challenging tasks for researchers. Diagnosis using miRNA biomarkers and treatment targeting miRNAs are useful strategies in the development of personalized medicine. Moreover, the sequence of many miRNAs is found to be conserved among different organisms. The exploration of miRNA conservation may be beneficial for developing antivirus therapy for variant viruses such as those of coronavirus. This Special Issue invites submissions of reviews and original papers that cover any innovative miRNA research, including the study of microRNA functionality via both biological and computational methods, clinical studies addressing miRNA biomarkers and miRNA evolution, and other related subjects.

Prof. Dr. Y-h. Taguchi
Prof. Dr. Hsiuying Wang
Topic Editors

Keywords

  • disease biomarker
  • identification of microRNA target genes
  • experimental methods that investigate miRNA functionality
  • computational methods that investigate miRNA functionality
  • miRNA pathway
  • miRNA conservation

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Biomolecules
biomolecules
5.5 8.3 2011 19.2 Days CHF 2700 Submit
Cells
cells
6.0 9.0 2012 18.8 Days CHF 2700 Submit
Genes
genes
3.5 5.1 2010 17.9 Days CHF 2600 Submit
International Journal of Molecular Sciences
ijms
5.6 7.8 2000 16.8 Days CHF 2900 Submit
Non-Coding RNA
ncrna
4.3 9.6 2015 17.9 Days CHF 1600 Submit

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Published Papers (8 papers)

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15 pages, 2627 KiB  
Article
A Comparative Analysis of MicroRNA Expression in Mild, Moderate, and Severe COVID-19: Insights from Urine, Serum, and Nasopharyngeal Samples
Biomolecules 2023, 13(12), 1681; https://doi.org/10.3390/biom13121681 - 21 Nov 2023
Viewed by 380
Abstract
COVID-19, caused by the SARS-CoV-2 virus, manifests with a wide range of clinical symptoms that vary from mild respiratory issues to severe respiratory distress. To effectively manage and predict the outcomes of the disease, it is important to understand the molecular mechanisms underlying [...] Read more.
COVID-19, caused by the SARS-CoV-2 virus, manifests with a wide range of clinical symptoms that vary from mild respiratory issues to severe respiratory distress. To effectively manage and predict the outcomes of the disease, it is important to understand the molecular mechanisms underlying its severity. This study focuses on analyzing and comparing the expression patterns of microRNAs (miRNAs) in serum, urine, and nasopharyngeal samples from patients with mild, moderate, and severe COVID-19. The aim is to identify potential associations with disease progression and discover suitable markers for diagnosis and prognosis. Our findings indicate the consistent upregulation of miR-21, miR-146a, and miR-155 in urine, serum, and nasopharyngeal samples from patients with mild COVID-19. In moderate cases, there were more significant changes in miRNA expression compared to mild cases. Specifically, miR-let-7 demonstrated upregulation, while miR-146b exhibited downregulation. The most notable alterations in miRNA expression profiles were observed in severe COVID-19 cases, with a significant upregulation of miR-223. Moreover, our analysis using Receiver-operating characteristic (ROC) curves demonstrated that miR-155, miR-let-7, and miR-223 exhibited high sensitivity and specificity, suggesting their potential as biomarkers for distinguishing COVID-19 patients from healthy individuals. Overall, this comparative analysis revealed distinct patterns in miRNA expression. The overlapping expression patterns of miRNAs in urine, serum, and nasopharyngeal samples suggest their potential utility in discriminating disease status. Full article
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17 pages, 5756 KiB  
Article
DAEMDA: A Method with Dual-Channel Attention Encoding for miRNA–Disease Association Prediction
Biomolecules 2023, 13(10), 1514; https://doi.org/10.3390/biom13101514 - 12 Oct 2023
Viewed by 615
Abstract
A growing number of studies have shown that aberrant microRNA (miRNA) expression is closely associated with the evolution and development of various complex human diseases. These key biomarkers’ identification and observation are significant for gaining a deeper understanding of disease pathogenesis and therapeutic [...] Read more.
A growing number of studies have shown that aberrant microRNA (miRNA) expression is closely associated with the evolution and development of various complex human diseases. These key biomarkers’ identification and observation are significant for gaining a deeper understanding of disease pathogenesis and therapeutic mechanisms. Consequently, pinpointing potential miRNA–disease associations (MDA) has become a prominent bioinformatics subject, encouraging several new computational methods given the advances in graph neural networks (GNN). Nevertheless, these existing methods commonly fail to exploit the network nodes’ global feature information, leaving the generation of high-quality embedding representations using graph properties as a critical unsolved issue. Addressing these challenges, we introduce the DAEMDA, a computational method designed to optimize the current models’ efficacy. First, we construct similarity and heterogeneous networks involving miRNAs and diseases, relying on experimentally corroborated miRNA–disease association data and analogous information. Then, a newly-fashioned parallel dual-channel feature encoder, designed to better comprehend the global information within the heterogeneous network and generate varying embedding representations, follows this. Ultimately, employing a neural network classifier, we merge the dual-channel embedding representations and undertake association predictions between miRNA and disease nodes. The experimental results of five-fold cross-validation and case studies of major diseases based on the HMDD v3.2 database show that this method can generate high-quality embedded representations and effectively improve the accuracy of MDA prediction. Full article
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21 pages, 5495 KiB  
Article
PLK1 Regulates MicroRNA Biogenesis through Drosha Phosphorylation
Int. J. Mol. Sci. 2023, 24(18), 14290; https://doi.org/10.3390/ijms241814290 - 19 Sep 2023
Viewed by 549
Abstract
Polo-Like Kinase 1 (PLK1), a key mediator of cell-cycle progression, is associated with poor prognosis and is a therapeutic target in a number of malignancies. Putative phosphorylation sites for PLK1 have been identified on Drosha, the main catalytic component of the microprocessor responsible [...] Read more.
Polo-Like Kinase 1 (PLK1), a key mediator of cell-cycle progression, is associated with poor prognosis and is a therapeutic target in a number of malignancies. Putative phosphorylation sites for PLK1 have been identified on Drosha, the main catalytic component of the microprocessor responsible for miR biogenesis. Several kinases, including GSK3β, p70 S6 kinase, ABL, PAK5, p38 MAPK, CSNK1A1 and ANKRD52-PPP6C, have been shown to phosphorylate components of the miR biogenesis machinery, altering their activity and/or localisation, and therefore the biogenesis of distinct miR subsets. We hypothesised that PLK1 regulates miR biogenesis through Drosha phosphorylation. In vitro kinase assays confirmed PLK1 phosphorylation of Drosha at S300 and/or S302. PLK1 inhibition reduced serine-phosphorylated levels of Drosha and its RNA-dependent association with DGCR8. In contrast, a “phospho-mimic” Drosha mutant showed increased association with DGCR8. PLK1 phosphorylation of Drosha alters Drosha Microprocessor complex subcellular localisation, since PLK1 inhibition increased cytosolic protein levels of both DGCR8 and Drosha, whilst nuclear levels were decreased. Importantly, the above effects are independent of PLK1’s cell cycle-regulatory role, since altered Drosha:DGCR8 localisation upon PLK1 inhibition occurred prior to significant accumulation of cells in M-phase, and PLK1-regulated miRs were not increased in M-phase-arrested cells. Small RNA sequencing and qPCR validation were used to assess downstream consequences of PLK1 activity on miR biogenesis, identifying a set of ten miRs (miR-1248, miR-1306-5p, miR-2277-5p, miR-29c-5p, miR-93-3p, miR-152-3p, miR-509-3-5p, miR-511-5p, miR-891a-5p and miR-892a) whose expression levels were statistically significantly downregulated by two pharmacological PLK1 kinase domain inhibitors, RO-5203280 and GSK461364. Opposingly, increased levels of these miRs were observed upon transfection of wild-type or constitutively active PLK1. Importantly, pre-miR levels were reduced upon PLK1 inhibition, and pri-miR levels decreased upon PLK1 activation, and hence, PLK1 Drosha phosphorylation regulates MiR biogenesis at the level of pri-miR-to-pre-miR processing. In combination with prior studies, this work identifies Drosha S300 and S302 as major integration points for signalling by several kinases, whose relative activities will determine the relative biogenesis efficiency of different miR subsets. Identified kinase-regulated miRs have potential for use as kinase inhibitor response-predictive biomarkers, in cancer and other diseases. Full article
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18 pages, 1903 KiB  
Review
MicroRNAs in the Regulation of RIG-I-like Receptor Signaling Pathway: Possible Strategy for Viral Infection and Cancer
Biomolecules 2023, 13(9), 1344; https://doi.org/10.3390/biom13091344 - 04 Sep 2023
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Abstract
The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play a crucial role as pattern-recognition receptors within the innate immune system. These receptors, present in various cell and tissue types, serve as essential sensors for viral infections, enhancing the immune system’s capacity to combat [...] Read more.
The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play a crucial role as pattern-recognition receptors within the innate immune system. These receptors, present in various cell and tissue types, serve as essential sensors for viral infections, enhancing the immune system’s capacity to combat infections through the induction of type I interferons (IFN-I) and inflammatory cytokines. RLRs are involved in a variety of physiological and pathological processes, including viral infections, autoimmune disorders, and cancer. An increasing body of research has examined the possibility of RLRs or microRNAs as therapeutic targets for antiviral infections and malignancies, despite the fact that few studies have focused on the regulatory function of microRNAs on RLR signaling. Consequently, our main emphasis in this review is on elucidating the role of microRNAs in modulating the signaling pathways of RLRs in the context of cancer and viral infections. The aim is to establish a robust knowledge base that can serve as a basis for future comprehensive investigations into the interplay between microRNAs and RIG-I, while also facilitating the advancement of therapeutic drug development. Full article
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19 pages, 2473 KiB  
Review
Common miRNAs of Osteoporosis and Fibromyalgia: A Review
Int. J. Mol. Sci. 2023, 24(17), 13513; https://doi.org/10.3390/ijms241713513 - 31 Aug 2023
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Abstract
A significant clinical association between osteoporosis (OP) and fibromyalgia (FM) has been shown in the literature. Given the need for specific biomarkers to improve OP and FM management, common miRNAs might provide promising tracks for future prevention and treatment. The aim of this [...] Read more.
A significant clinical association between osteoporosis (OP) and fibromyalgia (FM) has been shown in the literature. Given the need for specific biomarkers to improve OP and FM management, common miRNAs might provide promising tracks for future prevention and treatment. The aim of this review is to identify miRNAs described in OP and FM, and dysregulated in the same direction in both pathologies. The PubMed database was searched until June 2023, with a clear mention of OP, FM, and miRNA expression. Clinical trials, case–control, and cross-sectional studies were included. Gray literature was not searched. Out of the 184 miRNAs found in our research, 23 are shared by OP and FM: 7 common miRNAs are dysregulated in the same direction for both pathologies (3 up-, 4 downregulated). The majority of these common miRNAs are involved in the Wnt pathway and the cholinergic system and a possible link has been highlighted. Further studies are needed to explore this relationship. Moreover, the harmonization of technical methods is necessary to confirm miRNAs shared between OP and FM. Full article
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13 pages, 2609 KiB  
Article
mRNA-Seq and miRNA-Seq Analyses Provide Insights into the Mechanism of Pinellia ternata Bulbil Initiation Induced by Phytohormones
Genes 2023, 14(9), 1727; https://doi.org/10.3390/genes14091727 - 29 Aug 2023
Viewed by 498
Abstract
Pinellia ternata (Thunb.) Breit (abbreviated as P. ternata) is a plant with an important medicinal value whose yield is restricted by many factors, such as low reproductive efficiency and continuous cropping obstacles. As an essential breeding material for P. ternata growth and [...] Read more.
Pinellia ternata (Thunb.) Breit (abbreviated as P. ternata) is a plant with an important medicinal value whose yield is restricted by many factors, such as low reproductive efficiency and continuous cropping obstacles. As an essential breeding material for P. ternata growth and production, the bulbils have significant advantages such as a high survival rate and short breeding cycles. However, the location effect, influencing factors, and molecular mechanism of bulbil occurrence and formation have not been fully explored. In this study, exogenously applied phytohormones were used to induce in vitro petiole of P. ternata to produce bulbil structure. Transcriptome sequencing of mRNA and miRNA were performed in the induced petiole (TCp) and the induced bulbil (TCb). Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for the identification of key genes and pathways involved in bulbil development. A total of 58,019 differentially expressed genes (DEGs) were identified. The GO and KEGG analysis indicated that DEGs were mainly enriched in plant hormone signal transduction and the starch and sucrose metabolism pathway. The expression profiles of miR167a, miR171a, and miR156a during bulbil induction were verified by qRT-PCR, indicating that these three miRNAs and their target genes may be involved in the process of bulbil induction and play an important role. However, further molecular biological experiments are required to confirm the functions of the identified bulbil development-related miRNAs and targets. Full article
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17 pages, 3344 KiB  
Article
MicroRNAs Regulate Ca2+ Homeostasis in Murine Embryonic Stem Cells
Cells 2023, 12(15), 1957; https://doi.org/10.3390/cells12151957 - 28 Jul 2023
Viewed by 880
Abstract
MicroRNAs (miRNAs) are important regulators of embryonic stem cell (ESC) biology, and their study has identified key regulatory mechanisms. To find novel pathways regulated by miRNAs in ESCs, we undertook a bioinformatics analysis of gene pathways differently expressed in the absence of miRNAs [...] Read more.
MicroRNAs (miRNAs) are important regulators of embryonic stem cell (ESC) biology, and their study has identified key regulatory mechanisms. To find novel pathways regulated by miRNAs in ESCs, we undertook a bioinformatics analysis of gene pathways differently expressed in the absence of miRNAs due to the deletion of Dicer, which encodes an RNase that is essential for the synthesis of miRNAs. One pathway that stood out was Ca2+ signaling. Interestingly, we found that Dicer−/− ESCs had no difference in basal cytoplasmic Ca2+ levels but were hyperresponsive when Ca2+ import into the endoplasmic reticulum (ER) was blocked by thapsigargin. Remarkably, the increased Ca2+ response to thapsigargin in ESCs resulted in almost no increase in apoptosis and no differences in stress response pathways, despite the importance of miRNAs in the stress response of other cell types. The increased Ca2+ response in Dicer/ ESCs was also observed during purinergic receptor activation, demonstrating a physiological role for the miRNA regulation of Ca2+ signaling pathways. In examining the mechanism of increased Ca2+ responsiveness to thapsigargin, neither store-operated Ca2+ entry nor Ca2+ clearance mechanisms from the cytoplasm appeared to be involved. Rather, it appeared to involve an increase in the expression of one isoform of the IP3 receptors (Itpr2). miRNA regulation of Itpr2 expression primarily appeared to be indirect, with transcriptional regulation playing a major role. Therefore, the miRNA regulation of Itpr2 expression offers a unique mechanism to regulate Ca2+ signaling pathways in the physiology of pluripotent stem cells. Full article
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18 pages, 7164 KiB  
Article
Roles of miR-4442 in Colorectal Cancer: Predicting Early Recurrence and Regulating Epithelial-Mesenchymal Transition
Genes 2023, 14(7), 1414; https://doi.org/10.3390/genes14071414 - 08 Jul 2023
Viewed by 802
Abstract
Early recurrence in patients with colorectal cancer (CRC) is associated with a poor prognosis. We aimed to identify circulating microRNAs that are biomarkers of early CRC recurrence and elucidate their functions. We identified miR-4442 as a candidate biomarker by microRNA array analysis comparing [...] Read more.
Early recurrence in patients with colorectal cancer (CRC) is associated with a poor prognosis. We aimed to identify circulating microRNAs that are biomarkers of early CRC recurrence and elucidate their functions. We identified miR-4442 as a candidate biomarker by microRNA array analysis comparing preoperative and postoperative plasma levels in patients with CRC, with and without recurrence. The association between preoperative plasma miR-4442 levels, clinicopathological features, and recurrence-free survival was analyzed in 108 patients with CRC after curative surgery. Furthermore, cell-function analyses were performed, and the involvement of miR-4442 in regulating epithelial–mesenchymal transition (EMT) was examined. Preoperatively plasma miR-4442 levels were associated with CRC recurrence and exhibited an incremental increase with earlier recurrence dates. Moreover, miR-4442 demonstrated high sensitivity and specificity as a potential biomarker for early CRC recurrence. The expression of miR-4442 in cancer tissues of patients with metastatic liver cancer from CRC was higher than in normal liver, CRC, and normal colorectal tissues. The overexpression of miR-4442 promoted the proliferative, migratory, and invasive activities of CRC cells, decreased levels of RBMS1 and E-cadherin, and increased levels of N-cadherin and Snail1. Plasma miR-4442 is a clinically useful biomarker for predicting the early recurrence of CRC. Furthermore, miR-4442 regulates EMT in CRC by directly targeting the messenger RNA of RBMS1. Full article
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