PARPBP is a prognostic marker and confers anthracycline resistance to breast cancer

Abstract

Background: PARPBP (PARP1 binding protein) is an important suppressor of homologous recombination during DNA repair, but the expression and function of PARPBP in breast cancer remain unclear. Methods: PARPBP expression was analyzed in breast cancer patient samples and public datasets for its correlation with clinical outcome. The function of PARPBP in breast cancer cell proliferation and anthracycline treatment response were studied both in vitro and in vivo. Results: PARPBP was upregulated significantly at both mRNA and protein levels in breast cancer tissues compared with normal breast tissues. PARPBP high expression group had poorer overall survival (OS) than the PARPBP low expression group. Knockdown of PARPBP suppressed breast cancer cell proliferation and colony formation while overexpression of PARPBP did the opposite. We found that transcription factor forkhead box M1 (FOXM1) could activate PARPBP expression by directly binding to the promoter of PARPBP. In addition, high expression of PARPBP related with anthracycline resistance in breast cancer. Depletion of PARPBP increased breast cancer cell apoptosis and DNA damage caused by epirubicin. Moreover, tumor xenograft experiments further demonstrated that PARPBP was involved in breast cancer anthracycline resistance. Conclusion: Taken together, our results highlight that PARPBP is a prognostic marker and confers anthracycline resistance on breast cancer.