title: CBX8, a novel DNA repair protein, promotes tumorigenesis in human esophageal carcinoma.
abstract: DNA damage response and repair are carried out by certain proteins following damage by environmental clastogens, such as ionizing radiation and reactive oxygen species. It has been reported that many carcinomas that are characterized by resistance to chemotherapy and poor outcomes show dysfunction of these proteins. Chromobox homologue 8 (CBX8), a member of the polycomb group of proteins, has been identified as a factor that protects tumor cells from the detrimental effects of ionizing radiation (IR) or hydrogen peroxide (H2O2). In this study, we found that CBX8 was up-regulated in esophageal carcinoma tissues compared with adjacent non-cancerous tissues (P<0.01) and correlated with TNM stage in esophageal squamous cell carcinoma patients. Depletion of CBX8 decreased cell proliferation both in vitro and in vivo and increased the phosphorylation levels of p21, Wee1, and CHK1, which result in cyclin-dependent kinase inhibition and cell-cycle delay. CBX8 depletion also led to accumulation of spontaneous DNA damage and raised the sensitivity of tumor cells to IR or H2O2. We also found that the total level of CBX8 in the cells was increased after treating tumor cells with clastogens. In addition, our data showed that decreased CBX8 expression was accompanied by the reduction of EZH2 and EED, which have been reported to participate in DNA damage repair. Collectively, CBX8 might emerge as an oncogene for promoting the proliferation of tumor cells and raising the resistance of neoplasms to chemotherapy.
authors.affiliation: Department of Gynaecology and Obstetrics, Shanghai Tenth People's Hospital of Tongji University Shanghai 200072, China.
authors.forename: Weifan
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Clinical Laboratory, The Affiliated Tumor Hospital of Guangxi Medical University Nanning 530021, Guangxi Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ou
authors.affiliation: Department of Gynaecology and Obstetrics, Shanghai Tenth People's Hospital of Tongji University Shanghai 200072, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Gynaecology and Obstetrics, Shanghai Tenth People's Hospital of Tongji University Shanghai 200072, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xing
authors.affiliation: Department of Gynaecology and Obstetrics, Shanghai Tenth People's Hospital of Tongji University Shanghai 200072, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Yangpu District Central Hospital Shanghai 200433, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gynaecology and Obstetrics, Shanghai Tenth People's Hospital of Tongji University Shanghai 200072, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qiu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: C570428:CBX8 protein, human; D034741:RNA, Small Interfering; D063150:Polycomb Repressive Complex 1; D045643:DNA Repair Enzymes
keywords: CBX8; DNA repair; G2M cell cycle; esophageal carcinoma; tumorigenesis