MicroRNAs expressed in neuronal differentiation and their associated pathways: systematic review and bioinformatics analysis

Abstract MicroRNAs (miRNAs) plays an important role in the human brain from the embryonic period to adulthood. In this sense, they influence the development of neural stem cells (NSCs), regulating cellular differentiation and survival. Therefore, due to the importance of better comprehending the regulation of miRNAs in NSCs differentiation and the lack of studies that show the panorama of miRNAs and their signaling pathways studied until now we aimed to systematically review the literature to identify which miRNAs are currently being associated with neuronal differentiation and using bioinformatics analysis to identify their related pathways. A search was carried out in the following databases: Scientific Electronic Library Online (Scielo), National Library of Medicine National Institutes of Health (PubMed), Scopus, Web of Science and Science Direct, using the descriptors “(microRNA [MeSH])” and “(neurogenesis [MeSH])”. From the articles found, two independent and previously calibrated reviewers, using the EndNote X7 (Thomson Reuters, New York, NY, US), selected those that concern miRNA in the development of NSCs, based on in vitro studies. After, bioinformatic analysis was performed using the software DIANA Tools, mirPath v.3. Subsequently, data was tabulated, analyzed and interpreted. Among the 106 miRNAs cited by included studies, 55 were up-regulated and 47 were down-regulated. The bioinformatics analysis revealed that among the up-regulated miRNAs there were 24 total and 6 union pathways, and 3 presented a statistically significant difference (p ≤ 0.05). Among the down-regulated miRNAs, 46 total and 13 union pathways were found, with 7 presenting a significant difference (p ≤ 0.05). The miR-125a-5p, miR-423-5p, miR-320 were the most frequently found miRNAs in the pathways determined by bioinformatics. In this study a panel of altered miRNAs in neuronal differentiation was created with their related pathways, which could be a step towards understanding the complex network of miRNAs in neuronal differentiation.