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.

• Authors: De-Run Wang, Bing Wang, Ming Yang, Zhen-Lu Liu, Jing Sun, Yan Wang, Hui Sun, Liang-Jun Xie
• Journal: Biochemical genetics (Biochem Genet) Vol. 58 Issue 5 Pg. 691-704 (Oct 2020) ISSN: 1573-4927 [Electronic] United States
• PMID: 32419060 (Publication Type: Journal Article)

Chemical References

• MIRN30b microRNA, human
• MicroRNAs
• PPAR alpha
• PPARA protein, human

Topics

• Adult
• Case-Control Studies
• Hep G2 Cells
• Humans
• Lipid Metabolism
• Liver (metabolism, pathology)
• MicroRNAs (blood, metabolism)
• Non-alcoholic Fatty Liver Disease (metabolism)
• PPAR alpha (metabolism)