Cyclic adenosine monophosphate response element-binding protein transcriptionally regulates CHCHD2 associated with the molecular pathogenesis of hepatocellular carcinoma

The function of the novel cell migration-promoting factor, coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) in liver cancer remains to be elucidated. The aim of the present study was to elucidate the role of CHCHD2 in liver carcinogenesis. Immunohistochemistry was performed on patients with hepatocellular carcinoma (HCC) and suppression subtractive hybridization (SSH) was used for screening differentially expressed genes in the HepG2 cell cDNA library. Chronic hepatitis C virus (HCV) infection frequently leads to liver cancer. The HCV NS2 protein is a hydrophobic transmembrane protein that is associated with certain cellular proteins. Detailed characterization of the nonstructural protein 2 (NS2) of the HCV was performed with respect to its role in transregulatory activity in the HepG2 cell lines. A gel electrophoresis mobility shift assay and a chromatin immunoprecipitation assay were used to confirm the presence of cyclic adenosine monophosphate response element-binding protein (CREB), a transcriptional factor, which specifically interacts with the CHCHD2 promoter. CHCHD2 was highly expressed in the HCC specimens and was consistent with tumor markers of HCC. CHCHD2 was identified by SSH in the HepG2 cells. NS2 upregulated the expression of CHCHD2 by monitoring its promoter activities. The promoter of CHCHD2 contained 350 bp between nucleotides −257 and +93 and was positively regulated by CREB. In conclusion, the results of the present study indicated that CHCHD2 may be a novel biomarker for HCC and that CREB is important in the transcriptional activation of CHCHD2 by HCV NS2.