Hepatitis B virus upregulates cellular inhibitor of apoptosis protein 2 expression via the PI3K/AKT/NF‑κB signaling pathway in liver cancer

Lian,Jianping; Zou,Yuanhua; Huang,Ling; Cheng,Hao; Huang,Kai; Zeng,Junquan; Chen,Longhua

doi:10.3892/ol.2020.11267

Hepatitis B virus upregulates cellular inhibitor of apoptosis protein 2 expression via the PI3K/AKT/NF‑κB signaling pathway in liver cancer

Authors:
- Jianping Lian
- Yuanhua Zou
- Ling Huang
- Hao Cheng
- Kai Huang
- Junquan Zeng
- Longhua Chen
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Affiliations: Department of Radiation Oncology, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Rehabilitation, The Affiliated Hospital of Jinggangshan University, Ji'an, Jiangxi 343000, P.R. China, Department of Oncology, The Affiliated Hospital of Jinggangshan University, Ji'an, Jiangxi 343000, P.R. China, Department of Nasopharyngeal Carcinoma, The First People's Hospital of Chenzhou, Southern Medical University, Chenzhou, Hunan 423000, P.R. China, Department of Gastrointestinal Surgery, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
Published online on: January 8, 2020 https://doi.org/10.3892/ol.2020.11267
Pages: 2043-2052

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Abstract

Activation of antiapoptotic genes has been indicated as one of the factors that contributes to hepatitis B virus (HBV) infection‑induced liver cancer. The cellular inhibitor of apoptosis protein 2 (cIAP2), a member of the IAP family, is upregulated in various types of cancer and serves as a potential treatment target. However, to the best of our knowledge, the importance of cIAP2 in HBV‑induced liver cancer has not been investigated. In the present study, cIAP2 expression in liver cells in response to HBV infection and the underlying mechanism involved was investigated. Western blot analysis of clinical liver samples showed that higher cIAP2 expression was detected in HBV‑positive non‑cancerous tissue compared with that in HBV‑negative non‑cancerous tissue, and the expression was further increased in HBV‑positive liver cancer tissue. Reverse transcription‑quantitative PCR and western blot experiments performed on two liver cell lines also confirmed that cIAP2 expression was increased upon HBV infection at both the mRNA and protein levels. Promoter analysis revealed that HBV could activate cIAP2 promoter in an infection dose‑dependent manner, and this activation involved a NF‑κB‑binding site in the cIAP2 promoter. Further analysis demonstrated that HBV enhanced NF‑κB phosphorylation and nuclear translocation via the PI3K/AKT signaling pathway, leading to the binding and activation of cIAP2 promoter. The present data demonstrates that HBV‑infection induces cIAP2 expression in the liver by activation of the PI3K/AKT/NF‑κB signaling pathway through promoting the binding of NF‑κB to cIAP2 promoter, which may lead to carcinogenesis. The findings from the present study provide more information for understanding HBV‑induced liver cancer and also offer a potential target for treatment or diagnosis of this disease.

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