FOXM1 Modulates Cisplatin Sensitivity by Regulating EXO1 in Ovarian Cancer

• Published in: PloS one Vol. 9; no. 5; p. e96989
• Main Authors: Zhou, Jinhua, Wang, Yunfei, Wang, You, Yin, Xia, He, Yifeng, Chen, Lilan, Wang, Wenwen, Liu, Ting, Di, Wen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.05.2014; Public Library of Science (PLoS)
• Subjects: Apoptosis; Apoptosis - drug effects; Biology and life sciences; Breast cancer; Cancer; Cancer therapies; Cell cycle; Cell growth; Cell Line, Tumor; Chemoresistance; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Cisplatin - therapeutic use; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; DNA Repair - drug effects; DNA Repair Enzymes - metabolism; Drug Resistance, Neoplasm; Education; Exodeoxyribonucleases - metabolism; Female; Forkhead Box Protein M1; Forkhead Transcription Factors - metabolism; Gene expression; Gynecology; Hospitals; Humans; Kinases; Laboratories; Medicine; Medicine and Health Sciences; Obstetrics; Oncology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Ovary - drug effects; Ovary - metabolism; Ovary - pathology; Ribonucleic acid; RNA; Sensitivity; siRNA; Toxicity; Transcription factors; Up-Regulation; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096989

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.