MicroRNA-613 represses lipogenesis in HepG2 cells by downregulating LXR?.

ABSTRACT:

Background

MicroRNAs (miRNAs) emerge as new important regulators of lipid homeostasis by regulating corresponding genes. MiR-613 is a newly discovered microRNA, of which the biological function is unknown. A recent report has shown that miR-613 downregulates liver X receptor ? (LXR?), a ligand-activated nuclear receptor playing an important role in the regulation of lipid metabolism. The purpose of this study is to explore the effect and the molecular basis of miR-613 on lipogenesis in HepG2 cells.

Methods

HepG2 cells were transiently transfected with miR-613 mimic or control microRNA. Real time PCR, Western blot, Luciferase reporter assay and Oil Red O staining were employed to examine the expression of LXR? and its target genes involved in lipogenesis, binding site for miR-613 in 3'-untranslated region (3'-UTR) of LXR? mRNA and lipid droplet accumulation in the cells.

Results

MiR-613 dramatically suppressed the expression of LXR? and its target genes including sterol-regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), carbohydrate responsive element-binding protein (ChREBP) and acetyl-CoA carboxylase (ACC). Reporter assay showed that miR-613 directly bound to 3'-UTR of LXR? mRNA. Moreover, miR-613 significantly repressed LXR?-induced lipid droplet accumulation in HepG2 cells. Ectopic expression of LXR? without 3'-UTR markedly attenuated the miR-613-mediated downregulation of LXR?'s target genes and LXR?-induced lipid droplet accumulation.

Conclusions

MiR-613 suppresses lipogenesis by directly targeting LXR? in HepG2 cells, suggesting that miR-613 may serve as a novel target for regulating lipid homeostasis.

SUBMITTER: Zhong D 

PROVIDER: S-EPMC3605323 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature