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Fusion HBx from HBV integrant affects hepatocarcinogenesis through deregulation of ER stress response.
- Source :
-
Virus research [Virus Res] 2022 Jul 02; Vol. 315, pp. 198787. Date of Electronic Publication: 2022 Apr 14. - Publication Year :
- 2022
-
Abstract
- Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) worldwide. HBV X protein (HBx) is potentially the most oncogenic among HBV-encoding proteins, while HBV integration, which is frequently observed in HCC, contributes to HCC development. However, the molecular mechanism underlying HBV-induced hepatocarcinogenesis remains unclear. In this study, we identified the fusion HBx, the HBx-human fusion protein derived from HBV integrant, in Hep3B cells and investigated its role in hepatocarcinogenesis. The identified full-length fusion mRNA was 3,725 bp in length, and the fusion HBx, which consisted of 1-140 amino acids of HBx followed by 61 amino acids from the human genome, was translated from the fusion mRNA. The fusion HBx knockdown resulted in reduced cell proliferation and invasion, and loss of tumor development in nude mice. Moreover, the fusion HBx, but not wild HBx, provided anchorage-independent growth ability in soft agar although its transactivation ability was abrogated. Microarray analysis revealed that fusion HBx deregulated endoplasmic reticulum (ER) stress response by modifying ATF3, ATF4, and ATF6 transcription. Interestingly, the effects of fusion HBx on ER stress signaling pathway were similar to those of C-terminal truncated HBx, but significantly different from those of wild HBx. Our findings suggest that the fusion HBx plays a significant role in hepatocarcinogenesis by modifying ER stress response and could be an attractive target for the treatment of HBV-induced HCC.<br /> (Copyright © 2022. Published by Elsevier B.V.)
- Subjects :
- Amino Acids
Animals
Carcinogenesis genetics
Cell Line, Tumor
Hepatitis B virus metabolism
Humans
Mice
Mice, Nude
RNA, Messenger metabolism
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular virology
Endoplasmic Reticulum Stress
Hepatitis B
Liver Neoplasms genetics
Liver Neoplasms virology
Trans-Activators genetics
Viral Fusion Proteins genetics
Viral Regulatory and Accessory Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7492
- Volume :
- 315
- Database :
- MEDLINE
- Journal :
- Virus research
- Publication Type :
- Academic Journal
- Accession number :
- 35430320
- Full Text :
- https://doi.org/10.1016/j.virusres.2022.198787