Suppression of miR-30a-3p Attenuates Hepatic Steatosis in Non-alcoholic Fatty Liver Disease.

Abstract:

:Non-alcoholic fatty liver disease (NAFLD) have a high prevalence in humans in the past two decades. Here, we elucidated the functions of miR-30a-3p in the development of NAFLD and identified its potential targets. HepG-2 cells and NAFLD patients' blood samples were used in our study. Bioinformatics analysis as well as luciferase reporter assays were employed to distinguish peroxisome proliferator-activated receptor alpha (PPAR-α) as a target gene. Western blotting showed the expressions of lipid metabolic proteins and the target gene PPAR-α. Oil red O staining and triglyceride activity tested the fatty deposits after treatment with miR-30a-3p. miR-30a-3p was substantially up-regulated in NAFLD. Bioinformatics analyses showed that PPAR-α was a possible target of miR-30a-3p, linked with signaling pathways in NAFLD. PPAR-α as a novel target of miR-30a-3p, and suppression of its levels. The lipid metabolic-related proteins ACC, p-GSK-3β and FASN were up-regulated after transfecting with miR-30a-3p mimic, but the proteins CPT1, p-AMPK and UCP2 were down-regulated. miR-30a-3p inhibitor could diminish the protein manifestation of ACC, p-GSK-3β and FASN; and augment the protein manifestation of CPT1, p-AMPK and UCP2. On the contrary, overexpression of miR-30a-3p had adverse impacts on the performance of hepatocellular lipid accumulation and Triglyceride (TG) activity. Co-treatment with miR-30a-3p mimic and overexpression PPAR-α could revise the hepatic steatosis and the TG level induced by fat milk. Our findings suggest that miR-30a-3p/PPAR-α may be developed as a potential agent in NAFLD, which is enough to attenuate triglyceride accumulation and hepatic steatosis.

journal_name

Biochem Genet

journal_title

Biochemical genetics

authors

Wang DR,Wang B,Yang M,Liu ZL,Sun J,Wang Y,Sun H,Xie LJ

doi

10.1007/s10528-020-09971-0

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

691-704

issue

5

eissn

0006-2928

issn

1573-4927

pii

10.1007/s10528-020-09971-0

journal_volume

58

pub_type

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