Preprint Article Version 1 NOT YET PEER-REVIEWED

Regulation of ERK and AKT Pathways by Hepatitis B Virus X Protein via Notch1 Pathway in Hepatocellular Carcinoma

  1. Department of General Surgery, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuhan 430071, China
  2. Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China
Version 1 : Received: 21 September 2016 / Approved: 21 September 2016 / Online: 21 September 2016 (09:49:13 CEST)

How to cite: Liao, B.; Zhou, H.; Liang, H.; Li, C. Regulation of ERK and AKT Pathways by Hepatitis B Virus X Protein via Notch1 Pathway in Hepatocellular Carcinoma. Preprints 2016, 2016090074 (doi: 10.20944/preprints201609.0074.v1). Liao, B.; Zhou, H.; Liang, H.; Li, C. Regulation of ERK and AKT Pathways by Hepatitis B Virus X Protein via Notch1 Pathway in Hepatocellular Carcinoma. Preprints 2016, 2016090074 (doi: 10.20944/preprints201609.0074.v1).

Abstract

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

Subject Areas

hepatocellular carcinoma; hepatitis B virus X protein; Notch1 pathway; ERK; AKT

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