miR-93-5p promotes insulin resistance to regulate type 2 diabetes progression in HepG2 cells by targeting HGF

Insulin resistance is a common feature of type 2 diabetes mellitus (T2DM). However, the mechanisms underlying insulin resistance are not completely understood. The present study aimed to investigate the effect of microRNA (miR)-93-5p on insulin resistance in T2DM cells. Human hepatocellular carcinoma (HCC; HepG2) cells were cultured in medium with high glucose content (30 mM glucose) to establish an in vitro insulin-resistant cell model (IR group). Glucose consumption and glycogen synthesis assays were performed to assess glucose consumption and glycogen synthesis, respectively. By performing immunoprecipitation assays, the abundance of the Met-insulin receptor complex was detected in HepG2 cells. miR-93-5p and hepatocyte growth factor (HGF) mRNA expression levels were measured via reverse transcription-quantitative PCR, and HGF protein expression levels were measured via western blotting. A dual-luciferase reporter assay was conducted to investigate the interaction between miR-93-5p and HGF. Cell Counting Kit-8, BrdU and caspase-3 activity assays were performed to evaluate cell viability, proliferation and apoptosis, respectively, in insulin-resistant HepG2 cells following transfection with small interfering RNA-HGF, HGF overexpression vector, miR-93-5p mimic or miR-93-5p inhibitor. The results demonstrated that miR-93-5p expression was significantly increased and HGF expression was significantly decreased in HCC tissues isolated from patients with or without T2DM compared with adjacent healthy tissues isolated from patients without T2DM. Compared with the IR group, miR-93-5p overexpression significantly increased cell proliferation, glucose consumption and glycogen synthesis, but significantly inhibited apoptosis in insulin-resistant HepG2 cells. By contrast, compared with the IR group, HGF overexpression significantly inhibited cell proliferation, glucose consumption and glycogen synthesis, but significantly enhanced cell apoptosis in insulin-resistant HepG2 cells. Following co-transfection with HGF overexpression vector and miR-93-5p mimic, miR-93-5p mimic-mediated induction of HepG2 cell proliferation, glucose consumption and glycogen synthesis in insulin-resistant HepG2 cells was inhibited. Collectively, the results of the present study indicated that miR-93-5p enhanced insulin resistance to regulate T2DM progression in HepG2 cells by targeting HGF.