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- Title
Downregulation of transcription factor E4F1 in hepatocarcinoma cells: HBV-dependent effects on autophagy, proliferation and metabolism.
- Authors
Dai, Yayun; Cros, Marie-Pierre; Pontoizeau, Clément; Elena-Hermann, Bénédicte; Bonn, Günther K.; Hainaut, Pierre
- Abstract
E4F1, a factor involved in survival of somatic adult stem cells, is identified as a protein partner of the HBV oncoprotein HBx that contributes to maintain the viability and proliferation capacity of HBV-infected cells.The multifunctional E4F1 protein is a cellular target of the E1A adenoviral oncoprotein. Interaction between E4F1 and the hepatitis B virus (HBV) protein HBx has been demonstrated in vitro. In this study, RNA interference has been used to downregulate E4F1 in the hepatocellular carcinoma (HCC) cell line HepG2 (HBV negative) and its derivative, HBV expressing HepG2/2.2.15. Reduction of E4F1 levels induced hepatocyte vacuolation (formation of large cytoplasmic vesicles), increased autophagy and caused mitochondrial defects and metabolism changes in HepG2/2.2.15, but not in HepG2. Moreover, downregulation of E4F1 reduced DNA synthesis with partial cell cycle arrest in G1 in both cell types and this effect was more marked in HepG2/2.2.15 than in HepG2. These effects were partially prevented by RNA interference directed to either HBx or to p53. Coprecipitation and western blot experiments detected complexes between E4F1 and HBx in several HCC cell lines. Although a review of mutation and gene expression public databases did not support that E4F1 is specifically altered in liver cancer, our results suggest that E4F1 may neutralize the capacity of HBx to activate a p53-dependent, metabolic and growth arrest phenotype in liver cells, thus possibly contributing to the viability and proliferation of HBV-infected cells.
- Subjects
TRANSCRIPTION factors; LIVER cancer; CANCER cells; AUTOPHAGY; CELL proliferation; CELL metabolism; HEPATITIS B virus
- Publication
Carcinogenesis, 2014, Vol 35, Issue 3, p635
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgt353