B7-H3 upregulates BRCC3 expression, antagonizing DNA damage caused by 5-Fu

Sun,Zhang Zhang; Zhang,Ting; Ning,Kuan; Zhu,Ruan; Liu,Fen; Tang,Shou-Ching; Jiang,Bo; Hua,Dong

doi:10.3892/or.2016.4808

B7-H3 upregulates BRCC3 expression, antagonizing DNA damage caused by 5-Fu

Authors:
- Zhang Zhang Sun
- Ting Zhang
- Kuan Ning
- Ruan Zhu
- Fen Liu
- Shou-Ching Tang
- Bo Jiang
- Dong Hua
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Affiliations: Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China, Institute of Cancer, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China, 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, Gorgia Regents University Cancer Center, Augusta, GA 30912, USA
Published online on: May 13, 2016 https://doi.org/10.3892/or.2016.4808
Pages: 231-238

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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.

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