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

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

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)231-238
Number of pages8
JournalOncology Reports
Volume36
Issue number1
DOIs
StatePublished - Jul 2016

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Keywords

  • B7-H3
  • BRCC3
  • Colorectal cancer
  • DNA damage repair

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sun, Z. Z., Zhang, T., Ning, K., Zhu, R., Liu, F., Tang, S-C., Jiang, B., & Hua, D. (2016). B7-H3 upregulates BRCC3 expression, antagonizing DNA damage caused by 5-Fu. Oncology Reports, 36(1), 231-238. https://doi.org/10.3892/or.2016.4808