Suppression of miR-30a-3p Attenuates Hepatic Steatosis in Non-alcoholic Fatty Liver Disease.
De-Run WangBing WangMing YangZhen-Lu LiuJing SunYan WangHui SunLiang-Jun XiePublished in: Biochemical genetics (2020)
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.
Keyphrases
- fatty acid
- insulin resistance
- transcription factor
- signaling pathway
- end stage renal disease
- skeletal muscle
- cell proliferation
- pi k akt
- adipose tissue
- bioinformatics analysis
- genome wide
- peritoneal dialysis
- newly diagnosed
- type diabetes
- emergency department
- crispr cas
- gene expression
- prognostic factors
- liver fibrosis
- protein protein
- high throughput
- epithelial mesenchymal transition
- genome wide identification
- risk assessment
- dna methylation
- combination therapy
- binding protein
- replacement therapy
- electronic health record