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HBx induces HepG-2 cells autophagy through PI3K/Akt–mTOR pathway

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Abstract

Chronic hepatitis B virus infection is the dominant global cause of hepatocellular carcinoma (HCC), especially hepatitis B virus-X (HBx) plays a major role in this process. HBx protein promotes cell cycle progression, inactivates negative growth regulators, and binds to and inhibits the expression of p53 tumor suppressor gene and other tumor suppressor genes and senescence-related factors. However, the relationship between HBx and autophagy during the HCC development is poorly known. Previous studies found that autophagy functions as a survival mechanism in liver cancer cells. We suggest that autophagy plays a possible role in the pathogenesis of HBx-induced HCC. The present study showed that HBx transfection brought about an increase in the formation of autophagosomes and autolysosomes. Microtubule-associated protein light chain 3, Beclin 1, and lysosome-associated membrane protein 2a were up-regulated after HBx transfection. HBx-induced increase in the autophagic level was increased by mTOR inhibitor rapamycin and was blocked by treatment with the PI3K–Akt inhibitor LY294002. The same results can also be found in HepG2.2.15 cells. These results suggest that HBx activates the autophagic lysosome pathway in HepG-2 cells through the PI3K–Akt–mTOR pathway.

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Acknowledgments

The authors thank Prof. Shuang-ping Guo for providing the plasmids. We also thank Tao Tao for technical assistance.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, First Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China

    Peng Wang & Hai-xin Qian

  2. Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China

    Peng Wang, Qing-song Guo & Zhi-wei Wang

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  1. Peng Wang
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  2. Qing-song Guo
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  4. Hai-xin Qian
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Correspondence to Hai-xin Qian.

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Wang, P., Guo, Qs., Wang, Zw. et al. HBx induces HepG-2 cells autophagy through PI3K/Akt–mTOR pathway. Mol Cell Biochem 372, 161–168 (2013). https://doi.org/10.1007/s11010-012-1457-x

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  • DOI: https://doi.org/10.1007/s11010-012-1457-x

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