LncRNA NEAT1/microRNA-129-5p/SOCS2 axis regulates liver fibrosis in alcoholic steatohepatitis

Junfeng Ye,Yuanqiang Lin,Ying Yu,Di Sun

doi:10.1186/s12967-020-02577-5

Abstract

BackgroundLong 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).MethodsNEAT1, 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.ResultsMiR-129-5p was reduced while NEAT1 and SOCS2 were elevated in ASH. Inhibited NEAT1 or elevated miR-129-5p 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.ConclusionWe have found that the inhibited NEAT1 could suppress liver fibrosis in ASH mice by promoting miR-129-5p and restraining SOCS2, thereby decelerating the development of ASH.

Highlights

Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to play an essential role in non-alcoholic fatty liver disease
NEAT1 and suppressor of cytokine signaling 2 (SOCS2) are highly expressed while miR‐129‐5p is poorly expressed in serum of alcoholic steatohepatitis (ASH) patients The levels of corresponding indicators of ASH patients and healthy controls were evaluated (Table 2), and the results reflected that body mass index (BMI), ALT, AST, TC, TG, TNF-α, IL-1β and IL-6 levels were higher in ASH patients
ASH alcoholic steatohepatitis, BMI body mass index, ALT alanine aminotransferase, AST aspartate aminotransferase, TC total cholesterol, TG triglyceride, TNF-α tumor necrosis factor-α, IL-1β interleukin-1β, IL-6 interleukin-6 that (Fig. 1a, b) NEAT1 and SOCS2 levels were elevated while miR-129-5p expression was inhibited in ASH patients

Summary

Introduction

Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to play an essential role in non-alcoholic fatty liver disease. 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). NEAT1 promoted inflammatory response in sepsis-induced liver injury [8], and NEAT1 facilitated hepatic lipid accumulation and exacerbated NAFLD [9, 10]. This study was designed to elucidate the role of the NEAT1/ miR-129-5p/SOCS2 axis in the progression of ASH, and we inferred that the inhibited NEAT1 may repress liver fibrosis in ASH mice by regulating miR-129-5p and SOCS2

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