The effect of resveratrol on hyperglycaemia-related microRNAs in HepG2 cells

Background: Disruption in the normal functioning of specific micro ribonucleic acids (miRNAs), namely miR-30a-5p, miR-126-3p and miR-182-5p, is strongly linked to initiation and advancement of type 2 diabetes mellitus (T2DM). Aim: This study examined the effect of high glucose (HG) on the expression of selected miRNAs and their target genes in HepG2 cells and assessed the modulatory effects of resveratrol (RES), a polyphenol with known anti-diabetic properties. Setting: This was a laboratory-based study conducted at the South African Medical Research Council (SAMRC)/Cape Peninsula University of Technology (CPUT) Cardiometabolic Health Research Unit at the CPUT Bellville campus, Cape Town, South Africa. Methods: HepG2 cells were treated with HG (40 mM) and RES (low resveratrol [LR] 25 µM and high resveratrol [HR] 50 µM) for 48 h and 72 h. The expression levels of miR-30a-5p, miR-126-3p and miR-182-5p, and their target genes (Sprouty-related EVH1 domain containing 1 [SPRED1], Forkhead box O1 [FOXO1], Glucose-6-phosphatase [G6Pase], and Neuronal differentiation 1 [Neurod1]) were quantified using quantitative polymerase chain reaction (qPCR). Sirtuin 1 (SIRT1) messenger ribonucleic acid (mRNA) levels were also assessed, and the protein expression was measured using enzyme-linked immunosorbent assay (ELISA). Results: Exposure to HG for 48 h and 72 h decreased the expression of miR-126-3p and miR-182-5p, while increasing the expression level of its target genes SPRED1, FOXO1 and G6Pase. MiR-30a-5p was similarly decreased under HG, while Neurod1 expression was increased in HepG2 cells. RES treatment reversed these effects, restoring miRNA expression and decreasing their target genes. Additionally, HG decreased both mRNA and protein expression of SIRT1, while treatment with RES counteracted these effects, increasing SIRT1 expression. Conclusion: Our results suggest that RES may influence metabolic regulation and miRNA–gene interactions under HG conditions in HepG2 cells. Contribution: This study provides preliminary insights into mechanisms relevant to glucose-induced metabolic dysregulation.