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Biochem Biophys Res Commun. 2017 Nov 4;493(1):227-232. doi: 10.1016/j.bbrc.2017.09.042. Epub 2017 Sep 9.

MiR-181b regulates steatosis in nonalcoholic fatty liver disease via targeting SIRT1.

Author information

1
Department of Gastroenterology, The Second Hospital of Shandong University, Jinan, 250033, China.
2
Department of Gastroenterology, The Second Hospital of Shandong University, Jinan, 250033, China. Electronic address: jianqiang_guo1@126.com.

Abstract

Non-alcoholic fatty liver diseases (NAFLD) is one of the leading cause of chronic liver diseases in the world. However, the pathogenesis of NAFLD is still unclear. Emerging studies have demonstrated that microRNAs (miRs) are profoundly involved in NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-181b influences NAFLD via direct targeting SIRT1. The expression of miR181b was up-regulated while SIRT1 was down-regulated in both human NAFLD patients and high fat diet (HFD) induced NAFDL mice model. And palmitic acid (PA) treatment increased the miR-181b expression while decreased SIRT1 expression in HepG2 cells. Further, we identified that SIRT1 is a direct downstream target of miR-181b. Ectopic expression of miR-181b significantly repressed the 3'-UTR reporter activities of SIRT1 in a dose-dependent manner, while the effect of miR-181b was interrupted when the binding site of miR-181b within the SIRT1 3'-UTR was mutated. And overexpression of miR-181b reduced both the mRNA and protein levels of SIRT1 in HepG2 cells. We also found that inhibition of miR-181b expression alleviates hepatic steatosis both in vitro and in vivo. And the effect of miR-181b on steatosis was blocked by SIRT1 overexpression. Taken together, our data indicated that increased expression of miR-181b potentially contributes to altered lipid metabolism in NAFLD. Downregulation of miR-34a may be a therapeutic strategy against NAFLD by regulating its target SIRT1.

KEYWORDS:

MiR-181b; NAFLD; SIRT1; Steatosis

PMID:
28899784
DOI:
10.1016/j.bbrc.2017.09.042
[Indexed for MEDLINE]

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