Hbx induces the proliferation of hepatocellular carcinoma cells via ap1 over-expressed as a result of ER stress

Hyun Kook Cho, So Young Kim, Yi Yi Kyaw, Aye Aye Win, Seung-Hoi Koo, Hyeong Hoe Kim, Jaehun Cheong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and chronic hepatitis B virus (HBV) infection is the most common risk factor for HCC. The HBV proteins can induce oncogenic or synergy effects with a hyperproliferative response on transformation into HCC. CREBH (cAMP-responsive, element-binding protein H), activated by stress in the endoplasmic reticulum (ER), is an ER-resident transmembrane bZIP (basic leucine zipper) transcription factor that is specifically expressed in the liver. In the present study, we address the role played by CREBH activated by ER stress in HBV-induced hepatic cell proliferation. We confirmed CREBH activation by ER stress and showed that it occurred as a result of/via hepatitis B virus X (HBx)-induced ER stress. CREBH activated by HBx increased the expression of AP-1 target genes through c-Jun induction. Under pathological conditions such as liver damage or liver regeneration, activated CREBH may have an important role to play in hepatic inflammation and cell proliferation, as an insulin receptor with dual functions under these conditions. We showed that CREBH activated by HBx interacted with HBx protein, leading to a synergistic effect on the expression of AP-1 target genes and the proliferation of HCC cells and mouse primary hepatocytes. In conclusion, in HBVinfected hepatic cells or patients with chronic HBV, CREBH may induce proliferation of hepatic cells in co-operation with HBx, resulting in HCC. biochemj.

Original languageEnglish
Pages (from-to)115-121
Number of pages7
JournalBiochemical Journal
Volume466
DOIs
Publication statusPublished - 2015 Feb 15

Fingerprint

Endoplasmic Reticulum Stress
Viruses
Hepatitis B virus
Hepatocellular Carcinoma
Cells
Carrier Proteins
Hepatocytes
Liver
Transcription Factor AP-1
Chronic Hepatitis B
Cell proliferation
Genes
Cell Proliferation
Basic-Leucine Zipper Transcription Factors
jun Genes
Liver Regeneration
Insulin Receptor
Virus Diseases
Endoplasmic Reticulum
Chemical activation

Keywords

  • C-Jun
  • CAMP-responsive
  • Element-binding protein H
  • Er stress
  • Hepatitis B virus
  • Hepatitis B virus X
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Hbx induces the proliferation of hepatocellular carcinoma cells via ap1 over-expressed as a result of ER stress. / Cho, Hyun Kook; Kim, So Young; Kyaw, Yi Yi; Win, Aye Aye; Koo, Seung-Hoi; Kim, Hyeong Hoe; Cheong, Jaehun.

In: Biochemical Journal, Vol. 466, 15.02.2015, p. 115-121.

Research output: Contribution to journalArticle

Cho, Hyun Kook ; Kim, So Young ; Kyaw, Yi Yi ; Win, Aye Aye ; Koo, Seung-Hoi ; Kim, Hyeong Hoe ; Cheong, Jaehun. / Hbx induces the proliferation of hepatocellular carcinoma cells via ap1 over-expressed as a result of ER stress. In: Biochemical Journal. 2015 ; Vol. 466. pp. 115-121.
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