Hepatitis C virus nonstructural 5A protein inhibits the starvation‑induced apoptosis of hepatoblastoma cells by increasing Beclin 1 expression

Quan,Min; Liu,Shunai; Zhou,Li; Feng,Shenghu; Zhang,Yu; Cheng,Jun

doi:10.3892/or.2019.7060

Hepatitis C virus nonstructural 5A protein inhibits the starvation‑induced apoptosis of hepatoblastoma cells by increasing Beclin 1 expression

Authors:
- Min Quan
- Shunai Liu
- Li Zhou
- Shenghu Feng
- Yu Zhang
- Jun Cheng
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Affiliations: Department of Hepatology Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China
Published online on: March 13, 2019 https://doi.org/10.3892/or.2019.7060
Pages: 3051-3059

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Abstract

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) modulates cellular apoptosis, which is involved in the occurrence and development of liver cancer. The mechanisms of apoptosis inhibition by NS5A in liver cancer cells remains unclear. Beclin 1, which functions upstream of autophagosome formation, is upregulated by NS5A. Autophagy, an evolutionarily conserved catabolic process, has a crucial role in tumor initiation and progression. Autophagy was blocked by inhibitors 3‑methyladenine and chloroquine, or via knockdown of Beclin 1. Flow cytometric analysis and western blotting were used to detect apoptosis. It was found that inhibition of autophagy attenuated the NS5A‑mediated apoptosis inhibition of HepG2 cells. Furthermore, it was confirmed that Beclin 1 expression by NS5A was involved in the negative regulation of starvation‑induced liver cancer apoptosis, which was accompanied by reduced p53 and apoptosis regulator Bax expression, as well as decreased caspase‑3/-7 activation. Therefore, inhibition of autophagy may be promising therapeutic strategy in the treatment of HCV‑associated liver cancer.

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