Non-alcoholic fatty liver disease (
NAFLD) has emerged as a public health issue with a prevalence of 15-30% in Western populations and 6-25% in Asian populations. Certain studies have revealed the alteration of
microRNA (
miRNA or miR) profiles in
NAFLD and it has been suggested that miR-21 is associated with
NAFLD. In the present study, we measured the serum levels of miR-21 in patients with
NAFLD and also performed in vitro experiments using a cellular model of
NAFLD to further investigate the effects of miR-21 on
triglyceride and
cholesterol metabolism. Furthermore, a novel target through which miR-21 exerts its effects on
NAFLD was identified. The results revealed that the serum levels of miR-21 were lower in patients with
NAFLD compared with the healthy controls. In addition, 3-hydroxy-3-methylglutaryl-co-enzyme A
reductase (HMGCR) expression was increased in the serum of patients with
NAFLD both at the
mRNA and
protein level. To mimic the
NAFLD condition in vitro, HepG2 cells were treated with
palmitic acid (PA) and
oleic acid (OA). Consistent with the results obtained in the in vivo experiments, the expression levels of miR-21 were decreased and those of HMGCR were increased in the in vitro model of
NAFLD.
Luciferase reporter assay revealed that HMGCR was a direct target of miR-21 and that miR-21 exerted an effect on both HMGCR transcript degradation and protein translation. Furthermore, the results from the in vitro experiments revealed that miR-21 decreased the levels of
triglycerides (TG), free
cholesterol (FC) and total
cholesterol (TC) in the PA/OA-treated HepG2 cells and that this effect was attenuated by HMGCR overexpression. Taken together, to the best of our knowledge, the present study is the first to report that miR-21 regulates
triglyceride and
cholesterol metabolism in an in vitro model of
NAFLD, and that this effect is achieved by the inhibition of HMGCR expression. We speculate that miR-21 may be a useful
biomarker for the diagnosis and treatment of
NAFLD.