title: Cyclic adenosine monophosphate response element-binding protein transcriptionally regulates CHCHD2 associated with the molecular pathogenesis of hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Song
authors.affiliation: Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Biao
authors.initials: B
authors.lastname: Yang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Jinqian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Yixing
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Shunai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000302:isolation & purification / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D015854:Up-Regulation; D017361:Viral Nonstructural Proteins / Q000378:metabolism
chemical_list: C580880:CHCHD2 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C097010:NS2 protein, Hepatitis C virus; D014157:Transcription Factors; D017361:Viral Nonstructural Proteins