{"title":"Histone Modifier Differentially Regulates Gene Expression and Unravels Survival Role of MicroRNA-494 in Jurkat Leukemia.","authors":"Arathi Jayaraman, Tong Zhou, Sundararajan Jayaraman","doi":"10.2174/2211536610666210412153322","DOIUrl":"https://doi.org/10.2174/2211536610666210412153322","url":null,"abstract":"<p><strong>Background: </strong>Although the protein-coding genes are subject to histone hyperacetylation- mediated regulation, it is unclear whether microRNAs are similarly regulated in the T cell leukemia Jurkat.</p><p><strong>Objective: </strong>To determine whether treatment with the histone modifier Trichostatin A could concurrently alter the expression profiles of microRNAs and protein-coding genes.</p><p><strong>Methods: </strong>Changes in histone hyperacetylation and viability in response to drug treatment were analyzed, respectively, using western blotting and flow cytometry. Paired global expression profiling of microRNAs and coding genes was performed and highly regulated genes have been validated by qRT-PCR. The interrelationships between the drug-induced miR-494 upregulation, the expression of putative target genes, and T cell receptor-mediated apoptosis were evaluated using qRT-PCR, flow cytometry, and western blotting following lipid-mediated transfection with specific anti-microRNA inhibitors.</p><p><strong>Results: </strong>Treatment of Jurkat cells with Trichostatin A resulted in histone hyperacetylation and apoptosis. Global expression profiling indicated prominent upregulation of miR-494 in contrast to differential regulation of many protein-coding and non-coding genes validated by qRT-PCR. Although transfection with synthetic anti-miR-494 inhibitors failed to block drug-induced apoptosis or miR-494 upregulation, it induced the transcriptional repression of the PVRIG gene. Surprisingly, miR-494 inhibition in conjunction with low doses of Trichostatin A enhanced the weak T cell receptor- mediated apoptosis, indicating a subtle pro-survival role of miR-494. Interestingly, this prosurvival effect was overwhelmed by mitogen-mediated T cell activation and higher drug doses, which mediated caspase-dependent apoptosis.</p><p><strong>Conclusion: </strong>Our results unravel a pro-survival function of miR-494 and its putative interaction with the PVRIG gene and the apoptotic machinery in Jurkat cells.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":"10 1","pages":"39-50"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25582917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Younes El Founini, Imane Chaoui, Hind Dehbi, Mohammed El Mzibri, Roger Abounader, Fadila Guessous
{"title":"MicroRNAs: Key Regulators in Lung Cancer.","authors":"Younes El Founini, Imane Chaoui, Hind Dehbi, Mohammed El Mzibri, Roger Abounader, Fadila Guessous","doi":"10.2174/2211536610666210527102522","DOIUrl":"https://doi.org/10.2174/2211536610666210527102522","url":null,"abstract":"<p><p>Noncoding RNAs have emerged as key regulators of the genome upon gene expression profiling and genome-wide sequencing. Among these noncoding RNAs, microRNAs are short noncoding RNAs that regulate a plethora of functions, biological processes and human diseases by targeting the messenger RNA stability through 3'UTR binding, leading to either mRNA cleavage or translation repression, depending on microRNA-mRNA complementarity degree. Additionally, strong evidence has suggested that dysregulation of miRNAs contributes to the etiology and progression of human cancers, such as lung cancer, the most common and deadliest cancer worldwide. Indeed, by acting as oncogenes or tumor suppressors, microRNAs control all aspects of lung cancer malignancy, including cell proliferation, survival, migration, invasion, angiogenesis, cancer stem cells, immune-surveillance escape, and therapy resistance; and their expressions are often associated with clinical parameters. Moreover, several deregulated microRNAs in lung cancer are carried by exosomes and microvesicles and secreted in body fluids, mainly the circulation, where they conserve their stable forms. Subsequently, seminal efforts have been focused on extracellular microRNAs levels as noninvasive diagnostic and prognostic biomarkers in lung cancer. In this review, focusing on recent literature, we summarize the deregulation, mechanisms of action, functions and highlight clinical applications of miRNAs for better management and design of future lung cancer targeted therapies.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":"10 2","pages":"109-122"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39026055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Regulatory Network Played by miRNAs During Normal Pregnancy and Preeclampsia: A Comparative Study.","authors":"Héctor Ojeda-Casares, Irene Paradisi","doi":"10.2174/2211536611666211228100811","DOIUrl":"https://doi.org/10.2174/2211536611666211228100811","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a pregnancy-specific syndrome, characterized by hypertension, proteinuria, and edema. Affecting between 2% and 8% of gestations worldwide, it accounts for 10% to 15% of maternal deaths. Although its etiology remains unclear, it includes complex pathological processes involving microRNAs, small non-coding RNA molecules with post-transcriptional repression effects on target mRNAs.</p><p><strong>Objective: </strong>To assess the expression of miRNAs during normal pregnancies and those complicated by preeclampsia, a sample of Venezuelan women were studied.</p><p><strong>Method: </strong>Nine placental microRNAs (hsa-miR- 20a-5p, 21-3p, 26a-5p, 181a-5p, 199a-5p, 210-3p, 222-5p, 223-3p, 424-3p) were measured in maternal plasma during the second and third trimesters of normal pregnancies, using a SYBR Green®-based real-time PCR, and compared the results against women affected by preeclampsia.</p><p><strong>Results: </strong>All assessed miRNAs were detected in maternal plasma in pregnancies with and without preeclampsia. All except miR-222 were over-expressed during disease when compared to the second and to third-trimester controls. miR-20a, miR-21, miR-26a, and miR-223 were down-regulated in the third trimester in comparison to the second trimester in normal pregnancies.</p><p><strong>Conclusion: </strong>The variation of the miRNAs expression through normal pregnancies suggested their involvement in normal physiological pregnancy processes. In contrast, the significant deregulation of the nine studied miRNAs during preeclampsia indicated the involvement of their target genes in the pathogenesis of the disease. miR-199a and miR-21-3p showed the greatest changes in expression. This study shows for the first time the presence of miR-20a, miR-199, and miR-424 and the variations they undergo in the plasma of pregnant women with preeclampsia.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":"10 4","pages":"263-275"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39769424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The MicroRNA Days: The COVID-19 Pandemic from the Point of View of Short RNAs.","authors":"Alberto Izzotti","doi":"10.2174/2211536611666211228095628","DOIUrl":"https://doi.org/10.2174/2211536611666211228095628","url":null,"abstract":"<p><p>Despite their biological simplicity, microRNA-based organisms, such as RNA viruses, are currently shown to be unexpected threats to mammals, including humans. This situation is exemplified by the COVID-19 pandemic triggered by the spread of SARS-CoV-2. RNA viruses are older than DNA viruses. Indeed, from an evolutionary standpoint, RNA is an older molecule than DNA. The strength of RNA viruses, compared to DNA viruses, resides in their simplicity and instability. The instability of RNA viruses, such as human immunodeficiency virus (HIV) and flu viruses, generates mutants to escape the host's defense mechanisms. A formidable combination of lethality and infectivity was recently achieved by SARS-CoV-2. Complex DNAbased defense systems use Toll-like receptors to intercept viral RNA inside a cell. Activation of Toll-like receptors triggers inflammation and activates lymphocytes and monocytes, causing thromboxane release. In the case of SARS-CoV-2 infection, this process results in cytokine storms and lung thromboembolism. The ongoing pandemic can be envisioned as a struggle between highly evolved complex DNA organisms, i.e., humans, and poorly evolved simple RNA organisms, i.e., SARS-CoV-2 virus. Quite surprisingly, the complex organism has a serious problem defeating the simplistic organism. However, humans are finally developing a new effective weapon in fighting the SARS-CoV-2 virus, paradoxically, RNA-based vaccines. These considerations underscore the relevance of microRNAs as powerful tools in therapeutic and preventive medicine.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":"10 4","pages":"226-228"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39858124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vitamin D Regulates the Expression of Immune and Stress Response Genes in Dengue Virus-infected Macrophages by Inducing Specific MicroRNAs.","authors":"Geysson Javier Fernandez, Jorge Andrés Castillo, Diana Marcela Giraldo, Silvio Urcuqui-Inchima","doi":"10.2174/2211536610666211221151949","DOIUrl":"https://doi.org/10.2174/2211536610666211221151949","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis associated with Dengue virus (DENV) infection is marked by the impairment of host immune response. Consequently, the modulation of immune response has emerged as an important therapeutic target for the control of DENV infection. Vitamin D has been shown to regulate the immune response in DENV infection, although the molecular mechanism remains poorly understood. Post-transcriptional regulation of mRNA by miRNAs offers an opportunity to gain insight into the immunomodulation mediated by vitamin D.</p><p><strong>Objective: </strong>Previously, it has been observed that a high dose of vitamin D (4000 IU) decreased DENV-2 infection and inflammatory response in monocyte-derived macrophages (MDMs). Here, we examine whether high or low doses of vitamin D supplements exert differential effect on miRNA expression in DENV-infected macrophages.</p><p><strong>Methods: </strong>We analyzed miRNA expression profiles in MDMs isolated from healthy individuals who were given either 1000 or 4000 IU/day of vitamin D for 10 days. MDMs before or after vitamin D supplementation were challenged with DENV-2, and miRNAs profiles were analyzed by qPCR arrays.</p><p><strong>Results: </strong>DENV-2 infected MDMs supplemented with 4000 IU, showed up-regulation of miR-374a-5p, miR-363-3p, miR-101-3p, miR-9-5p, miR-34a-5p, miR-200a-3p, and the family of miRNAs miR-21-5p, and miR-590-p. The miRNA profile and predicted target mRNAs suggested regulatory pathways in MDMs obtained from healthy donors who received higher doses of vitamin D. These DENV-2 infected MDMs expressed a unique set of miRNAs that target immune and cellular stress response genes.</p><p><strong>Conclusion: </strong>The results suggest vitamin D dose-dependent differential expression of miRNAs target key signaling pathways of the pathogenesis of dengue disease.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":"10 4","pages":"240-249"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39862216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cervantes-Ayala Andrea Viridiana, Velázquez-Flores Miguel Ángel, Ruiz Esparza-Garrido Ruth
{"title":"MicroRNAs: Beyond Post-transcriptional Regulation of mRNAs.","authors":"Cervantes-Ayala Andrea Viridiana, Velázquez-Flores Miguel Ángel, Ruiz Esparza-Garrido Ruth","doi":"10.2174/2211536611666211228102045","DOIUrl":"https://doi.org/10.2174/2211536611666211228102045","url":null,"abstract":"<p><p>MicroRNAs (miRNAs), small non-coding RNAs, participate in the transcriptional and post-transcriptional regulation of eukaryotic genes, and are potential biomarkers for diseases. Mature miRNAs can be located in both the nucleus and cytoplasm, where they perform their regulatory function. The discovery of new miRNAs and the identification of their targets and functions are fundamental to understanding the biological processes regulated by them, as well as the role they play in diseases. This present study researched miRNAs function at nuclear level and as circulating molecules.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":"10 4","pages":"229-239"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39769425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MiR-147: Functions and Implications in Inflammation and Diseases.","authors":"Ling Lin, Kebin Hu","doi":"10.2174/2211536610666210707113605","DOIUrl":"https://doi.org/10.2174/2211536610666210707113605","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are small non-coding RNAs (19~25 nucleotides) that regulate gene expression at a post-transcriptional level through repression of mRNA translation or mRNA decay. MiR-147, which was initially discovered in mouse spleen and macrophages, has been shown to correlate with coronary atherogenesis and inflammatory bowel disease and modulate macrophage functions and inflammation through TLR-4. Altered miR-147 level has been shown in various human diseases, including infectious disease, cancer, cardiovascular disease, neurodegenerative disorder, etc. This review will focus on the current understanding regarding the role of miR-147 in inflammation and diseases.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":"10 2","pages":"91-96"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714690/pdf/nihms-1753310.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39164883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association Between miR-146a rs2910164 Polymorphism and Breast Cancer Susceptibility: An Updated Meta-Analysis of 9545 Cases and 10030 Controls.","authors":"Abdolkarim Moazeni-Roodi, Sajjad Aftabi, Sahel Sarabandi, Shima Karami, Mohammad Hashemi, Saeid Ghavami, Mohsen Taheri","doi":"10.2174/2211536610666210707113229","DOIUrl":"https://doi.org/10.2174/2211536610666210707113229","url":null,"abstract":"<p><strong>Background: </strong>Several studies have reported a possible association of miR-146a rs2910164 polymorphism with Breast Cancer (BC) development. However, the correlation between this polymorphism and susceptibility to BC is under debate. The current meta-analysis was designed and performed to more conclusively evaluate the miR-146a rs2910164 polymorphism and its potential link to BC.</p><p><strong>Methods: </strong>Our team has selected eligible studies (published up to October 2, 2020) from several electronic databases, including Web of Science, PubMed, Scopus and Google Scholar. A total number of 9,545 BC cases and 10,030 controls extracted from 26 eligible articles were included in this study. We utilized pooled Odds Ratios (ORs) as well as 95% confidence intervals (95% CIs) under five genetic models for quantitative estimation of any possible association between miR-146a rs2910164 polymorphism and BC.</p><p><strong>Results: </strong>Based on this meta-analysis, our findings suggest that there is no significant association between miR-146a rs2910164 polymorphism and BC risk. However, stratified analysis revealed that the rs2910164 polymorphism significantly increased the risk of BC in hospital-based studies using the homozygous genetic model (OR=1.37, 95%CI=1.01-1.86, p=0.043, CC vs. GG). Neither Asian nor Caucasian populations showed any significant association between rs2910164 polymorphism and BC susceptibility.</p><p><strong>Conclusion: </strong>In summary, our findings suggest that BC development is not associated with miR-146a rs2910164 polymorphism. However, larger ingenious future investigations might be needed for a more precise estimation of any association between miR-146a rs2910164 polymorphism and BC.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":"10 3","pages":"191-199"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39164967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}