LncRNA NEAT1/microRNA-129-5p/SOCS2 axis regulates liver fibrosis in alcoholic steatohepatitis
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Journal of Translational Medicine Open Access
RESEARCH
LncRNA NEAT1/microRNA‑129‑5p/ SOCS2 axis regulates liver fibrosis in alcoholic steatohepatitis Junfeng Ye1, Yuanqiang Lin2, Ying Yu1 and Di Sun3*
Abstract Background: Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to play an essential role in non-alcoholic fatty liver disease. However, the role of NEAT1 in regulation of alcoholic steatohepatitis (ASH) remains largely unknown. This study aims to explore the role of NEAT1 in ASH by mediating microRNA-129-5p (miR-129-5p) targeting suppressor of cytokine signaling 2 (SOCS2). Methods: NEAT1, miR-129-5p and SOCS2 expression in serum of ASH patients were assessed. In the in vitro cellular experiment, we transfected siRNAs, oligonucleotides or plasmids into ethanol-induced AML-12 mouse hepatocytes to alter NEAT1 and miR-129-5p expression, and inflammatory factors and lipid content were determined. In the in vivo animal experiment, we injected lentiviruses carrying siRNAs, oligonucleotides or plasmids onto ASH mice (ASH induced by feeding mice a Lieber-DeCarli ethanol diet) to alter NEAT1 and miR-129-5p expression through the tail vein. Serum liver function, blood lipids and inflammatory factors were detected; liver histopathology, liver cell apoptosis, and fibrosis were observed. The relationship between NEAT1 and miR-129-5p, or between miR-129-5p and SOCS2 was verified. Results: MiR-129-5p was reduced while NEAT1 and SOCS2 were elevated in ASH. Inhibited NEAT1 or elevated miR129-5p suppressed the elevated lipid metabolism and restrained inflammation reaction in ethanol-stimulated AML-12 cells. The promoted miR-129-5p and inhibited NEAT1 could improve the liver function and repress blood lipid, inflammation reaction, hepatocyte apoptosis and liver fibrosis in ethanol-induced ASH mice. Furthermore, NEAT1 could negatively regulate miR-129-5p to target SOCS2. Conclusion: We have found that the inhibited NEAT1 could suppress liver fibrosis in ASH mice by promoting miR129-5p and restraining SOCS2, thereby decelerating the development of ASH. Keywords: Alcoholic steatohepatitis, Long non-coding RNA nuclear paraspeckle assembly transcript 1, MicroRNA129-5p, Suppressor of cytokine signaling 2, Liver fibrosis Background As the largest solid organ, liver serves as a pivotal role in metabolism and detoxication in human body. Liver injury is the main cause that greatly contributes to the *Correspondence: [email protected] 3 Department of Colorectal & Anal Surgery, First Hospital, Jilin University, No. 71 Xinmin street, Changchun 130021, Jilin, People’s Republic of China Full list of author information is available at the end of the article
risk of human health globally, especially in Asian countries [1]. Second to viral hepatitis, alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the commonest liver diseases in developed countries [2]. ALD is a deleterious result of excessive alcohol consumption, resulting in a great burden and a loss of socioeconomic p
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