Role of the microRNA‑214/Bax axis in the progression of acute liver failure

Wu,Shaohong; Huang,Xiaoping; Sun,Wei; Chen,Li; Huang,Yan; Wang,Yan; Luo,Erping; Qin,Ailan; Zhao,Weifeng; Gan,Jianhe

doi:10.3892/mmr.2020.11123

Role of the microRNA‑214/Bax axis in the progression of acute liver failure

Authors:
- Shaohong Wu
- Xiaoping Huang
- Wei Sun
- Li Chen
- Yan Huang
- Yan Wang
- Erping Luo
- Ailan Qin
- Weifeng Zhao
- Jianhe Gan
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Affiliations: Department of Infectious Diseases, The First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215006, P.R. China
Published online on: May 5, 2020 https://doi.org/10.3892/mmr.2020.11123
Pages: 117-126
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute liver failure (ALF) is a fatal liver disease characterized by severe hepatocyte destruction. MicroRNAs (miRNAs/miRs) have been reported to serve a key role in a number of liver diseases. Therefore, the aim of the present study was to investigate the role and underlying mechanism of miR‑214 in ALF. ALF murine and hepatocyte models were established using D‑galactosamine (D‑GalN) and lipopolysaccharide (LPS) or D‑GalN + tumor necrosis factor (TNF)‑α, respectively. The expression levels of miR‑214 and Bax were detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and/or western blotting. Furthermore, an automatic biochemical analyzer was used to measure the levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT). The levels of TNF‑α and interleukin (IL)‑6 were detected by ELISA and RT‑qPCR. In addition, TUNEL staining and flow cytometry were used to analyze cell apoptosis, and the protein expression of caspase‑3 was determined by western blotting. It was identified that the levels of AST and ALT were increased and that hepatocyte apoptosis was enhanced in the D‑GalN/LPS‑stimulated group compared with the control. Furthermore, higher expression of caspase‑3 was observed in the D‑GalN/LPS‑stimulated group. In addition, it was demonstrated that miR‑214 was downregulated, while Bax was upregulated in D‑GalN/LPS‑stimulated mice and D‑GalN/TNF‑α‑stimulated BNLCL2 cells. Moreover, in D‑GalN/TNF‑α‑stimulated BNLCL2 cells, miR‑214 overexpression suppressed apoptosis and decreased TNF‑α and IL‑6 levels, and these effects were reversed by the Bax plasmid. It was also identified that overexpression of miR‑214 significantly decreased Bax mRNA and protein expression levels in vitro. Collectively, the present results suggested that miR‑214 inhibited hepatocyte apoptosis during ALF development via targeting Bax, thus indicating that miR‑214 may be a potential target for ALF treatment.

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