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

Abstract

Abstract Background: PARPBP (PARP1 Binding Protein) is an important homologous recombination inhibitor of human cells during DNA repair. But the expression and function of PARPBP in breast cancer remain unclear.Methods: We evaluated the expression and prognostic value of PARPBP in breast cancer by immunohistochemical analysis in our patients (n=137) and public available datasets. Multiple in vitro and in vivo animal models characterized its functions.Results: In the present study, we demonstrated that PARPBP was significantly upregulated in breast cancer tissues compared with normal breast tissues. PARPBP high expression group had poor overall survival (OS) compared to the PARPBP low expression group. Similar results got in TCGA and KM Plotter overall survival analysis. Knockdown of PARPBP suppressed breast cancer cell growth proliferation and colony formation. Furthermore, we found that high expression of PARPBP related with chemotherapy resistance in breast cancer. Depletion of PARPBP increases breast cancer cell apoptosis and DNA damage caused by chemotherapy drugs. Transcription factor forkhead box M1(FOXM1) activated PARPBP expression by directly binding to the promoter of PARPBP. Moreover, tumor xenograft experiments further demonstrated that PARPBP was involved in breast cancer chemoresistance. Conclusions: Taken together, our results highlight PARPBP is a prognostic marker and confers chemotherapeutic resistance to breast cancer.