Argonaute protein assisted drug discovery for miRNA-181c-5p and target gene ATM translation repression: a computational approach.

The miRNA binds to AGO's seed region, prompting the exploration of small molecules that can offset miRNA repression of target mRNA. This miRNA-181c-5p was found to be upregulated in the chronic traumatic encephalopathy, a prevalent neurodegenerative disease in contact sports and military personals. The research aimed to identify compounds that disrupt the AGO-assisted loop formation between miRNA-181c-5p and ATM, consequently repressing the translation of ATM. Target genes from commonly three databases (DIANA-microT-CDS, miRDB, RNA22 and TargetScan) were subjected to functional annotation and clustering analysis using DAVID bioinformatics tool. Haddock server were employed to make miRNA-181c-5p:ATM-AGO complex. A total of 2594 small molecules were screened using Glide XP based on their highest binding affinity towards the complex, through a three-phase docking approach. The top 5 compounds (DB00674-Galantamine, DB00371-Meprobamate, DB00694-Daunorubicin, DB00837-Progabide, and DB00851-Dacarbazine) were further analyzed for stability in the miRNA-181c-5p:ATM-AGO-ligand complex interaction using GROMACS (version 2023.2). Hence, these findings suggest that these molecules hold potential for facilitating AGO-assisted repression of ATM gene translation.

A meta-analysis of differentially expressed circulatory micro-RNAs in chronic traumatic encephalopathy and other tauopathies: A significant role of miR-181c-5p.

BACKGROUND: Micro-RNA (miRs) targeting kinases and phosphatases regulate the hyper-phosphorylation of tau protein, which is a characteristic feature of Chronic Traumatic Encephalopathy (CTE). PRIMARY OBJECTIVE: Identification of lead dysregulated miR expressed in CTE, and other similar tauopathies. METHODS: A search strategy was devised using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to mine into multiple indexing databases such as Web of Science, Google Scholar, and PubMed spanning from 2005 to June 2022. Seven articles were screened out of 34,221 publications based on inclusion criteria and were categorized into two groups i.e., (1) CTE and its risk factors and (2) Age-related neurodegenerative disorders. RESULTS: Statistical analysis [RevMan 5.4.1] results showed that the overall risk ratio (RR) of the first group is significant (RR = 0.62, 95% CI = [0.38, 1.00], z = 1.95, p = 0.05) whereas, the second group favours the control population (RR = 1.64, 95% CI = [0.85, 3.16], z = 1.14, p = 0.14). CONCLUSION: We observed that among all other dysregulated miRs, miR-181c-5p is significantly overexpressed in Alzhimers disease (AD) and CTE. Further, we found that miR-210-3p is also upregulated notably in all groups. In sum, we conclude that these miRs can be considered as potential target and biomarker in the diagnosis and treatment of various tauopathies.

Meta-analysis of Circulatory mitomiRs in stress Response: Unveiling the significance of miR-34a and miR-146a.

BACKGROUND: MicroRNAs (miRNAs) are short, noncoding RNAs with essential roles in cellular pathways and are often associated with various diseases and stress conditions. Recently, they have been discovered in mitochondria, termed "mitomiRs," with unique functions. Mitochondria, crucial organelles for energy production and stress responses, Dysregulated mitomiRs functions and expression has been evident in stress conditions such as cardiovascular and neurodegenerative. In this meta-analysis we have systematically identified miR-34a & miR-146a as possible potential biomarkers for affliction. METHODS: A meta-analysis was conducted to assess the potential role of miR-34a and miR-146a, two specific mitomiRs, as biomarkers in stress-related conditions. The study followed PRISMA guidelines, involving comprehensive database searches in May and September 2023. Twelve studies meeting predefined inclusion criteria were selected, and data analysis included the evaluation of miR-34a and miR-146a expression levels in various stress conditions compared to control groups. We also performed Gene ontology (GO) and Pathway enrichment analysis to observe how mitomiRs affects our body. RESULTS: The meta-analysis revealed a significant increase in overall mitomiRs (miR-34a and miR-146a) expression levels in experimental groups experiencing different stress conditions compared to control groups (Z = 3.54, p < 0.05 using RevMan software). miR-34a demonstrated more pronounced upregulation and exhibited potential as a specific biomarker in certain stress-related conditions (Z = 2.22, p < 0.05). However, miR-146a did not show a significant difference, requiring further investigation in various stress-related contexts. The Analysis indicated a high degree of heterogeneity among the studies. CONCLUSION: This meta-analysis emphasises the importance of mitomiRs, especially miR-34a, as potential biomarkers in the intricate interplay between stress, mitochondrial function, and disease. The study opens new avenues for exploring miRNAs' diagnostic and therapeutic applications in stress-related diseases, highlighting their pivotal role at the crossroads of molecular biology, psychology, and medicine.