title: B7-H3 upregulates BRCC3 expression, antagonizing DNA damage caused by 5-Fu.
abstract: 5-fluorouracil (5-Fu) is still recognized as the mainstay in colorectal cancer chemotherapy, but the response rate of 5-Fu in colorectal cancer is less than 50%. Our previous mRNA microarray data revealed that BRCC3, a component of the BRCA1-BRCA2-BRCC3 DNA repair complex, had a direct relationship with B7-H3, an immunoglobulin that is upregulated in tumor tissue and associated with metastasis and poor prognosis. Real-time PCR and western blot analysis confirmed that the expression of both BRCC3 mRNA and protein, respectively, were elevated following B7-H3 overexpression in SW480 cells; likewise, BRCC3 expression decreased after B7-H3 was knocked down in HCT-8 cells. DNA comet assay results indicate an inverse correlation between the extent of 5-Fu-induced DNA damage and the expression level of B7-H3 in both SW480- and HCT-8-based cell lines. In SW480 cells that overexpress B7-H3, knockdown of BRCC3 similarly permitted greater 5-Fu-induced DNA damage. Altogether, results suggest that BRCC3 may play a role in B7-H3-induced 5-Fu resistance, such that B7-H3 upregulates BRCC3 expression, enhancing DNA repair in colorectal cancer cells.
authors.affiliation: Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Zhang Zhang
authors.initials: ZZ
authors.lastname: Sun
authors.affiliation: Institute of Cancer, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Ning
authors.affiliation: Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine, Jiangsu Higher Education Institutions, Suzhou, Jiangsu, P.R. China.
authors.forename: Ruan
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Institute of Cancer, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Gorgia Regents University Cancer Center, Augusta, GA 30912, USA.
authors.forename: Shou-Ching
authors.initials: SC
authors.lastname: Tang
authors.affiliation: Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
mesh_terms: D060887:B7 Antigens / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D000072017:Deubiquitinating Enzymes; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
chemical_list: D060887:B7 Antigens; C423237:CD276 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; C518017:BRCC3 protein, human; D000072017:Deubiquitinating Enzymes; D005472:Fluorouracil