Profiling the 8-nucleotide microRNA targets in genes involved in type 2 diabetes mellitus in association with oxidative and endoplasmic reticulum stress

Abstract

Type 2 diabetes mellitus (T2DM) is one of the top 10 global killers. The association between oxidative stress and T2DM has been reported, in which oxidative stress triggers the life-threatening consequences, including stroke, nephropathy, and myocardial infarction. MicroRNA (miRNA)-based therapies are thought to revolutionize early medical interventions, potentially enabling the treatment of T2DM. miRNAs are 20-22 nucleotide non-coding sequences used to silence genes at the post-transcriptional level. Gene testing registry, TargetScan, and other bioinformatic databases were used to identify the oxidative- and endoplasmic reticulum (ER) stress-linked genes and their targeted miRNAs (8-mers and species conserved) associated with T2DM. ShinyGO was used to establish links between T2DM and its associated genes. We identified putative common miRNAs, such as miR-26-5p/miR-124-3p.1/miR-124-3p.2/miR-98-5p/miR-17-5p/miR-519-3p/miR-20-5p/miR-93-5p/miR-106-5p, which may involve in the regulation of T2DM-associated genes. In addition, several common miRNAs were also considered in the regulation of pathological conditions. The miRNAs for T2DM associated with oxidative stress are as follows: miR-33-5p/miR-506-3p/miR-7-5p/miR-107/miR-93-5p, and for T2DM associated with ER stress are as follows: miR-195-5p/miR-181-5p/miR-101-3p.1/miR-424-5p/miR-145-5p/miR-519-3p/miR-16-5p. Overall, this study provides a framework for the rational selection of miRNAs for nucleic acid-based therapies and guides future studies in maximizing the potential of miRNAs against oxidative- and ER-stress associated with T2DM.

Keywords

miRNAs / Type 2 diabetes mellitus / Oxidative stress / Endoplasmic reticulum stress

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