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 journalArticlepeer-review

24 Citations (Scopus)


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
Publication statusPublished - 2015 Feb 15

Bibliographical note

Publisher Copyright:
© 2015 Biochemical Society.


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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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