MicroRNAs expressos durante a cicatrização da pele e vias de sinalização associadas: uma revisão sistemática e análise bioinformática

Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules made up of approximately 22 nucleotides, and are, mainly, responsible for regulating gene expression at the posttranscriptional level. MiRNAs can be related to several biological processes of the organism, such as skin healing. Healing is a complex biological process, consisting of four phases: hemostasis, inflammation, proliferation, and remodeling. Parallel to this, consequences related to chronic wounds or any wounds that do not present efficient healing have been increasingly reported, especially in the longer-lived population. Furthermore, they are already considered an important public health problem. In view of this, a better understanding of miRNAs and the signaling pathways associated with wound healing can atenuate the problem related to chronic wounds and can be applied in studies aimed at the development of new therapies. Therefore, due to the need to better understand the role of miRNAs involved in skin wound healing, the aim of this study was to systematically review the available literature in order to identify miRNAs and their respective signaling pathways associated with skin wound healing. For this, an electronic search was carried out in the following databases: National Library of Medicine National Institutes of Health (PubMed), Science Direct, Scifinder, Scopus and Web of Science, using the descriptors: “(microRNA [MeSH])” and “(skin [MeSH])” and “(wound healing [MeSH])”. A total of 3,227 potential articles were found and were later exported to the Zotero reference manager. Then, two independent and previously calibrated reviewers completed the step of excluding duplicate references. After applying the eligibility criteria in the articles, those related to the analysis of miRNA expression in healing in animals in vivo were selected. Finally, bioinformatics analyzes were performed using DIANA Tools software, mirPath v.3. Soon, the data obtained were analyzed and interpreted. Bioinformatics analysis revealed that on day 1, among the miRNAs with increased expression, there were 13 binding signaling pathways, eight of which were statistically significant. Among the miRNAs with decreased expression, even on day 1, 17 union pathways were found, 12 of which were statistically significant. While on day 5, among miRNAs with increased expression, 16 binding pathways were found, 12 of which were statistically significant. Finally, among the miRNAs with decreased expression, 15 binding pathways were found, 11 of which were statistically significant. Through this systematic review, it was possible to develop an overview of miRNAs and better understand how they can be altered in wound healing. Although considerable heterogeneity was observed among the selected studies, it is possible to identify which miRNAs and signaling pathways are involved in the healing process. Thus, the results obtained, in addition to providing a better understanding of miRNAs and their mechanism of action – focusing on the skin wound healing process –, hereafter, they may be applied in possible new therapeutic approaches.