The cancer-testis gene,MEIOB,sensitizes triple-negative breast cancer to PARP1 inhibitors by inducing homologous recombination deficiency

作     者：Yayun Gu Cheng Wang Rongxuan Zhu Jianshui Yang Wenwen Yuan Yanhui Zhu Yan Zhou Na Qin Hongbing Shen Hongxia Ma Hongxia Wang Xiaoan Liu Zhibin Hu Yayun Gu;Cheng Wang;Rongxuan Zhu;Jianshui Yang;Wenwen Yuan;Yanhui Zhu;Yan Zhou;Na Qin;Hongbing Shen;Hongxia Ma;Hongxia Wang;Xiaoan Liu;Zhibin Hu

作者机构：State Key Laboratory of Reproductive MedicineCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentJiangsu Collaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211116China Department of BioinformaticsSchool of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing 211166China Department of OncologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Department of Breast SurgeryThe First Affiliated Hospital with Nanjing Medical UniversityNanjing 210029China 

出 版 物：《Cancer Biology & Medicine》 (癌症生物学与医学（英文版）)

年 卷 期：2021年第18卷第1期

页      面：74-87页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.81902836 and 81572602) the China Postdoctoral Science Foundation(Grant Nos.2017M610339 and 2018M630584) 

主　　题：Cancer-testis gene MEIOB triple-negative breast cancer PARP1 inhibitor cell proliferation 

摘      要：Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)*** this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of *** regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human *** effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in ***-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 ***:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially *** activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC *** analysis showed that MEIOB participated in DSB repair in ***,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with ***,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX ***:MEIOB played an oncogenic role in TNBC through its involvement in *** addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.