miR-203 Inhibits Alcohol-Induced Hepatic Steatosis by Targeting Lipin1

Abstract

Alcoholic liver disease (ALD) is a global liver disease which characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Alcohol abuse is one of the main reasons for liver disease. Alcoholic fatty liver (AFL) disease is the early stage of ALD and associated with the excessive lipids accumulation in hepatocytes as well as oxidative stress. MicroRNA-203 (miR-203) is known to suppress the proliferation and metastasis of hepatocellular carcinoma, but the role in the progression of alcoholic liver disease is not clear and is warranted for further investigation. In the present study, we have found the expression of miR-203 is down-regulated in Gao-Binge alcoholic mice model and ethanol-induced AML-12 cell lines in vitro. Furthermore, over-expression of miR-203 decrease the lipids accumulation in liver and ethanol-induced AML-12 cells. Mechanistically, we identified that Lipin1 is a key regulator of hepatic lipid metabolism, and acts as a downstream target for miR-203. In summary, our results suggested that over-expression of miR-203 inhibited the liver lipids accumulation and the progression of AFL by targeting Lipin1.

MicroRNAs as systemic biomarkers to assess distress in animal models for gastrointestinal diseases

“…In line with our results, a significant downregulation of miR-203 was also observed in mice after induction of alcoholic induced liver damage 39 . Out of the 4 miRNA candidates exclusively miR-132 was significantly upregulated after induction of all gastrointestinal diseases ( Fig.…”

“…This study also suggested that a high level of miR-203 aggravates the cerulein induced cell injury through suppression of nuclear factor interleukin-3 38 . In line with our results, a significant downregulation of miR-203 was also observed in mice after induction of alcoholic induced liver damage 39 .…”

Modulation of hepatic miRNA expression in Atlantic salmon (Salmo salar) by family background and dietary fatty acid composition

“…One species‐specific mature miRNA (ssa‐miR‐nov1‐5p) and the teleost‐specific miR‐462b‐5p were among the DE miRNAs, indicating they may have regulatory roles in the salmon lipid metabolism. All the remaining 10 evolutionary‐conserved DE miRNAs have been identified as miRNAs that are important in lipid metabolism and/or adipogenesis in other vertebrates (Ahn et al ., 2013; Arner & Kulyte, 2015; Chen et al ., 2014; Cheng et al ., 2018; Hu et al ., 2012; Shin et al ., 2014; Ye et al ., 2014). In most cases their particular functions have not been experimentally established but rather assumed from target gene predictions.…”

Integrated Analyses Identify Key Molecules and Reveal the Potential Mechanism of miR-182-5p/FOXO1 Axis in Alcoholic Liver Disease

“…Normal liver cell L02 line was obtained from the Laboratory Medicine of Chongqing Medical University (Chongqing, China) and cultured in RPMI 1640 (Gibco, United States) supplemented with 10% fetal bovine serum (Gibco, United States) and 100 U/ml Penicillin-Streptomycin Solution (Thermo Fisher Scientific, China). After reaching 50–60% confluence, L02 cells were stimulated with 100 mM alcohol medium for 48 h to construct the ALD cell model ( 9 , 13 ). All cells were grown at 37°C in a humidified incubator containing 5% CO 2 .…”

“…For instance, miR-30b-5p promotes hepatocellular carcinoma (HCC) cell growth, proliferation, and metastasis by targeted inhibition of inositol polyphosphate phosphatase 1 expression ( 8 ). In ALD, over-expression of miR-203 decreases hepatic lipid accumulation by targeting the Lpin1 gene (Lipin1) ( 9 ). Silencing miR-21 decreases cytokine production and inflammatory responses in alcohol-induced hepatitis ( 10 ).…”