CBX8, a novel DNA repair protein, promotes tumorigenesis in human esophageal carcinoma.

نویسندگان

  • Weifan Xiao
  • Chao Ou
  • Jinlong Qin
  • Feng Xing
  • Yi Sun
  • Zhi Li
  • Jin Qiu
چکیده

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.

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عنوان ژورنال:
  • International journal of clinical and experimental pathology

دوره 7 8  شماره 

صفحات  -

تاریخ انتشار 2014