J Cancer 2019; 10(17):4142-4150. doi:10.7150/jca.30493 This issue

Research Paper

HBV Integration-mediated Cell Apoptosis in HepG2.2.15

Xiaoge Hu1,2,#, Jiahong Jiang1,#, Chao Ni1,3,#, Qiuran Xu1,2, Song Ye4, Junjie Wu1,2, Feimin Ge5, Yong Han1,2, Yinyuan Mo6, Dongsheng Huang1,2,3✉, Liu Yang1,2,✉

1. Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P. R. China.
2. Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P. R. China.
3. Department of General surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P. R. China.
4. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Secondary Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P. R. China.
5. Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P. R. China.
6. Department of Pharmacology/Toxicology and Cancer Institute, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
#These authors contributed equally to this work.

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Citation:
Hu X, Jiang J, Ni C, Xu Q, Ye S, Wu J, Ge F, Han Y, Mo Y, Huang D, Yang L. HBV Integration-mediated Cell Apoptosis in HepG2.2.15. J Cancer 2019; 10(17):4142-4150. doi:10.7150/jca.30493. Available from https://www.jcancer.org/v10p4142.htm

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Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the second leading cause of cancer deaths in the word. Hepatitis B virus (HBV) infection plays an important role in the development of HCC. However, the mechanisms by which HBV integration affects host cells remain poorly understood. HepG2.2.15 cell line is derived from HCC cell line HepG2 with stable transfection HBV expression. In this study, HepG2.2.15 cells showed decreased proliferation, G1 cell cycle arrest and increased apoptosis, when compared to HepG2 cells. HBV capture sequencing was conducted in both genome and transcriptome level, followed by RNA expression sequencing in HepG2.2.15. Here, CAMSAP2/CCDC12/DPP7/OR4F3 were found to be targets for HBV integration in both genome and transcriptome level, accompanied by alteration in their expression when compared to HepG2. Among these genes, DPP7 was the only one gene with HBV integration into its exon, meanwhile DPP7 expression level was also downregulated in HepG2.2.15 as compared to HepG2. Furthermore, DPP7 knockdown resulted in increased apoptosis through upregulation of the Bax/Bcl2 ratio in HepG2 cells. Our results suggest that HBV integration of DPP7 was involved in cell apoptosis.

Keywords: HepG2.2.15, viral integration, Hepatitis B virus, proliferation, cell cycle, apoptosis