title: Molecular mechanism of hepatitis B virus (HBV) on suppression of raf kinase inhibitor protein (RKIP) expression.
abstract: Raf kinase inhibitor protein (RKIP) has been shown to be a suppressor of the mitogen-activated protein kinase pathway and is reported to be involved in human malignancy. However, the molecular mechanism of hepatitis B virus (HBV) in regulating RKIP expression is not yet clarified. In this study, we compared RKIP expression in 107 pairs of matched liver cancer and adjacent non-cancerous liver tissues. Among seven HBV-encoded proteins, we found HBV X (HBX) protein could significantly inhibit the expression level of RKIP, indicating that HBV could suppress RKIP expression through regulating HBX. To further elucidate the mechanism, analyses on transcriptional regulation and promoter methylation inhibition were conducted in Huh7 cells. Our results showed that HBX can interact with AP1 protein to inhibit the RKIP transcription. Moreover, we observed that the promoter methylation level of RKIP could be enhanced by HBV. In conclusion, our study revealed that RKIP could act as a molecular marker for HBV-infected liver cancer, but had no tumor-suppressing effect.
authors.affiliation: Center for Evidence-Based Medicine, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Cheng
authors.affiliation: Department of General Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi 435000, Hubei Province, China.
authors.forename: Guo-Zheng
authors.initials: GZ
authors.lastname: Yu
authors.affiliation: Center for Evidence-Based Medicine, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.|Department of Urology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.affiliation: Center for Evidence-Based Medicine, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.|Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.
authors.forename: Xue-Qun
authors.initials: XQ
authors.lastname: Ren
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000150:complications / Q000821:virology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D012333:RNA, Messenger; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: AP1protein; HBV; RKIP; liver cancer; promoter methylation