FOXM1通过调控卵巢癌中的EXO1来调节顺铂敏感性。
FOXM1 modulates cisplatin sensitivity by regulating EXO1 in ovarian cancer.
作者信息
Zhou Jinhua, Wang Yunfei, Wang You, Yin Xia, He Yifeng, Chen Lilan, Wang Wenwen, Liu Ting, Di Wen
机构信息
Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, China; Focus Construction Subject of Shanghai Education Department, Shanghai, China; Shanghai Health Bureau Key Disciplines and Specialties Foundation, Shanghai, China; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, China; Focus Construction Subject of Shanghai Education Department, Shanghai, China; Shanghai Health Bureau Key Disciplines and Specialties Foundation, Shanghai, China.
出版信息
PLoS One. 2014 May 13;9(5):e96989. doi: 10.1371/journal.pone.0096989. eCollection 2014.
Cisplatin is commonly used in ovarian cancer chemotherapy, however, chemoresistance to cisplatin remains a great clinical challenge. Oncogenic transcriptional factor FOXM1 has been reported to be overexpressed in ovarian cancer. In this study, we aimed to investigate the potential role of FOXM1 in ovarian cancers with chemoresistance to cisplatin. Our results indicate that FOXM1 is upregulated in chemoresistant ovarian cancer samples, and defends ovarian cancer cells against cytotoxicity of cisplatin. FOXM1 facilitates DNA repair through regulating direct transcriptional target EXO1 to protect ovarian cancer cells from cisplatin-mediated apoptosis. Attenuating FOXM1 and EXO1 expression by small interfering RNA, augments the chemotherapy efficacy against ovarian cancer. Our findings indicate that targeting FOXM1 and its target gene EXO1 could improve cisplatin effect in ovarian cancer, confirming their role in modulating cisplatin sensitivity.
顺铂常用于卵巢癌化疗，然而，对顺铂的化疗耐药性仍然是一个巨大的临床挑战。据报道，致癌转录因子FOXM1在卵巢癌中过度表达。在本研究中，我们旨在探讨FOXM1在对顺铂耐药的卵巢癌中的潜在作用。我们的结果表明，FOXM1在化疗耐药的卵巢癌样本中上调，并保护卵巢癌细胞免受顺铂的细胞毒性。FOXM1通过调节直接转录靶点EXO1促进DNA修复，以保护卵巢癌细胞免受顺铂介导的凋亡。通过小干扰RNA减弱FOXM1和EXO1的表达，可增强对卵巢癌的化疗疗效。我们的研究结果表明，靶向FOXM1及其靶基因EXO1可以提高顺铂在卵巢癌中的疗效，证实了它们在调节顺铂敏感性中的作用。
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