Dysregulation of miR-642a-5p is involved in the regulation of pancreatic β-cell function via Mef2d

Abstract

Despite extensive research on miR-642a-5p, its specific function in pancreatic β-cells and its contribution to the pathogenesis of type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to investigate the regulatory role of miR-642a-5p in pancreatic β-cells (EndoC-βH1) and its association with the transcription factor Mef2d. Differentially expressed miRNAs related to T2DM were identified through analysis of the GSE70318 dataset. Based on predictions from the TargetScan, miRDB, miWalk, and miRTarBase databases, the interaction between miR-642a-5p and Mef2d was validated using dual-luciferase reporter assays and gene interference experiments. In EndoC-βH1 cells treated with high glucose and palmitic acid, cell apoptosis, insulin secretion, and the expression of related genes were evaluated. The functional impact of co-transfection with miR-642a-5p and Mef2d on EndoC-βH1 cells was also analyzed. Results indicated that miR-642a-5p was abnormally expressed in the GSE70318 dataset, and Mef2d was confirmed as its target gene. Overexpression of miR-642a-5p promoted insulin secretion, upregulated insulin secretion-related genes, enhanced cell viability, inhibited cell apoptosis, reduced malondialdehyde (MDA) levels, suppressed Bax and Nox4 expression, and upregulated Bcl-2 and Sod2. These effects were reversed by Mef2d overexpression. Conversely, inhibition of miR-642a-5p impaired insulin secretion, downregulated Ins1 and Pdx1, reduced cell viability, promoted cell apoptosis, increased MDA levels, promoted Bax and Nox4 expression, and suppressed Bcl-2 and Sod2. These effects were reversed upon Mef2d silencing. In summary, miR-642a-5p protects EndoC-βH1 cells from apoptosis by targeting Mef2d and regulating cellular function and oxidative stress levels.