期刊
AUTOPHAGY
卷 17, 期 12, 页码 4423-4441出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2021.1917948
关键词
ARRB1; autophagy; cell cycle; hepatocellular carcinoma; hepatitis B virus X protein
类别
资金
- National Natural Science Foundation of China [82070574, 81602122]
- Natural Science Foundation Team Project of Guangdong Province [2018B030312009]
- Breeding Foundation for Young Pioneers' Research of Sun Yatsen University [17ykpy53]
- Young Teacher Foundation of Sun Yat-sen University [17ykpy53]
The protein ARBB1 plays a critical role in HBV-related hepatocellular carcinoma by modulating autophagy and the CDKN1B-CDK2-CCNE1-E2F1 axis, suggesting it may be a potential therapeutic target for HCC.
The hepatitis B virus X protein (HBx) is involved in the process of hepatocellular carcinoma via the activation of various oncogenes. Our previous study indicated that ARBB1 (arrestin beta 1) promotes hepatocellular carcinogenesis (HCC). However, the role of ARRB1 in HBx-related HCC remains unclear. Herein, we identified that ARRB1 was upregulated by HBx in vivo and in vitro. Arrb1 deficiency suppressed HBx-induced hepatocellular carcinogenesis in several mouse models. Furthermore, knockdown of ARRB1 blocked HBx-induced macroautophagic/autophagic flux and disrupted the formation of autophagosomes. ARRB1 interacted with HBx, and the autophagic core protein MAP1LC3/LC3, a scaffolding protein, was essential for complete autophagy. Inhibition of autophagy by 3-methyladenine or interference of ATG5 or ATG7 attenuated HBx-induced cell cycle acceleration and the subsequent proliferative response via the induction of G(1)/S arrest. The absence of autophagy abolished the phosphorylation of CDK2 and the activity of the CDK2-CCNE1 complex. Our results demonstrate that ARRB1 plays a critical role in HBV-related HCC via modulating autophagy and the CDKN1B-CDK2-CCNE1-E2F1 axis and indicate that ARRB1 may be a potential therapeutic target for HCC.
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