Mechanism of LncRNA NEAT1 deficiency aggravating acetaminophen-induced acute liver injury

Abstract

Abstract: Objective The aim of this study was to investigate the molecular role of long non-coding ribonucleic acid (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in the pathogenesis of acetaminophen (APAP)-induced acute liver injury.Methods In our study, 8 C57BL/6 mice were randomly divided into experimental group and control group, with 4 mice in each group. Acute liver injury was induced by intraperitoneal injection of APAP. The mouse liver tissue RNA was extracted to detect the expression of lncRNA NEAT1. Mouse primary hepatocytes were extracted and cultured. In experimental group, hepatocytes were treated with small interfering ribonucleic acid (siRNA) to knock down lncRNA NEAT1, and then stimulated with APAP. The expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in cell culture supernatant is dectected to evaluate the degree of damage, together with histological analysis. Results In vivo, ALT (7565 ± 763.3 vs 42.75 ± 2.3, P<0.05) and AST (7718 ± 901.6 vs 45.05 ± 4.1, P<0.05) were significantly higher in the APAP-treated group than control group. The expression of lncRNA NEAT1 in liver tissues of the APAP-treated group was 3 times higher than that of control group (P<0.05). In vitro experiments, lncRNA NEAT1 expression was significantly increased after APAP stimulation in primary hepatocyte medium for 24 hours. ALT and AST in the supernatant of hepatocytes in the experimental group treated by siRNA and APAP were significantly higher than those in control group.Conclusion Our results indicate that knockdown of lncRNA NEAT1 can exacerbate APAP-induced acute liver injury, suggesting the potential benefit of lncRNA NEAT1 in the prevention and treatment of APAP-induced acute liver injury in the clinic.

Key words: Acetaminophen, LncRNA NEAT1, Acute liver injury

ZHAO Jie, ZHONG Cheng-peng, CAI Jie, ZHANG Jian-jun. Mechanism of LncRNA NEAT1 deficiency aggravating acetaminophen-induced acute liver injury[J]. Chinese Hepatolgy, 2019, 24(12): 1393-1395.

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