Hepatitis B virus X protein induces expression of alpha-fetoprotein and activates PI3K/mTOR signaling pathway in liver cells

• DOI: 10.18632/oncotarget.2906
• Publication Date: 2015-09-15T06:34:31Z
• Authors: Mingyue Zhu; Junli Guo; Wei Li; Yan Lu; Shigan Fu; Xieju Xie; Hua Xia; Xu Dong; Yi Chen; Ming Quan; Shaojiang Zheng; Keping Xie; Mengsen Li
• Keywords: HBx; Liver Cancer

// Mingyue Zhu 1, 2, * , Junli Guo 3, Wei Li 2 Yan Lu Shigan Fu 1 Xieju Xie 4 Hua Xia Xu Dong Yi Chen Ming Quan 3 Shaojiang Zheng 5 Keping Mengsen Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Medical College, Haikou, 571199, P. R. China Molecular Biology, Department Gastroenterology, Hepatology & Nutrition, The University Texas MD Anderson Cancer Center, Houston, TX 77030, USA Physiology Pathophysiology, Tumor Institute, Affiliated Hospital 570102, These authors have contributed equally to this work Correspondence to: Li, e-mail: [e-mail] Xie, [e-mail] Keywords: AFP, HBx, PI3K/mTOR signaling, Liver cells, Hepatocarcinogenesis Received: October 10, 2014      Accepted: December 11, Published: January 21, 2015 ABSTRACT hepatitis B virus (HBV)-X protein (HBx) induces malignant transformation liver elevated expression alpha-fetoprotein (AFP) is a significant biomarker hepatocarcinogenesis. However, the role AFP in HBV-related hepatocarcinogenesis unclear. In study, we investigated regulatory impact on HBx-mediated human hepatocytes. We found that HBV induced before oncogenes, e.g ., Src, Ras chemokine (C-X-C motif) receptor (CXCR4), activated kinase (AKT) mammalian target rapamycin (mTOR) HCC tissues cells transfected with HBx. Cytoplasmic interacted inhibited phosphatase tensin homolog deleted chromosome 10 (PTEN), activating phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway promoting mTOR-mediated stimulation transcription factor hypoxia inducible factor-1α (HIF-1α), therefore led activation promoters CXCR4, genes. On contrary, reduced by siRNA resulted repression p-mTOR, pAKT, cells. Taken together, for first time our study indicates HBx-induced critically promote through signaling.