Crosstalk between microRNAs, the putative target genes and the lncRNA network in metabolic diseases

Abstract

MicroRNA s (miRNA s/miRs) are small non-coding RNA s (ncRNA s) that regulate gene expression. Emerging knowledge has suggested that miRNA s have a role in the pathogenesis of metabolic disorders, supporting the hypothesis that miRNA s may represent potential biomarkers or targets for this set of diseases. However, the current evidence is often controversial. Therefore, the aim of the present study was to determine the associations between miRNA s-target genes, miRNA- long ncRNA s (lncRNA s), and miRNA s-small molecules in human metabolic diseases, including obesity, type 2 diabetes and non-alcoholic fatty liver disease. The metabolic disease-related miRNA s were obtained from the Human MicroRNA Disease Database (HMDD) and miR2Disease database. A search on the databases Matrix Decomposition and Heterogeneous Graph Inference (MDHGI) and DisGeNE T were also performed. miRNA s target genes were obtained from three independent sources: Microcosm, TargetScan and miRTarBase. The interactions between miRNA s-lncRNA and miRNA- small molecules were performed using the miRN et web tool. The network analyses were performed using Cytoscape software. As a result, a total of 20 miRNA s were revealed to be associated with metabolic disorders in the present study. Notably, 6 miRNA s (miR- 17-5p, miR- 29c-3p, miR- 34a-5p, miR- 103a-3p, miR- 107 and miR- 132-3p) were found in the four resources (HMDD, miR2Disease, MDHGI, and DisGeNE T) used for these analyses, presenting a stronger association with the diseases. Furthermore, the target genes of these miRNA s participate in several pathways previously associated with metabolic diseases. In addition, interactions between miRNA- lncRNA and miRNA- small molecules were also found, suggesting that some molecules can modulate gene expression via such an indirect way. Thus, the results of this data mining and integration analysis provide further information on the possible molecular basis of the metabolic disease pathogenesis as well as provide a path to search for potential biomarkers and therapeutic targets concerning metabolic diseases.