FOXM1 Modulates Cisplatin Sensitivity by Regulating EXO1 in Ovarian Cancer

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 o...

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Published inPloS 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
LanguageEnglish
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
Online AccessGet full text

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Abstract 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.
AbstractList 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.
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.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.
Author He, Yifeng
Wang, Yunfei
Zhou, Jinhua
Chen, Lilan
Wang, Wenwen
Di, Wen
Wang, You
Yin, Xia
Liu, Ting
AuthorAffiliation 2 Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, China
1 Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
3 Focus Construction Subject of Shanghai Education Department, Shanghai, China
University of Texas Health Science Center at San Antonio, United States of America
5 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
4 Shanghai Health Bureau Key Disciplines and Specialties Foundation, Shanghai, China
AuthorAffiliation_xml – name: 2 Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, China
– name: 5 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
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– name: 4 Shanghai Health Bureau Key Disciplines and Specialties Foundation, Shanghai, China
– name: 1 Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
– name: University of Texas Health Science Center at San Antonio, United States of America
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/24824601$$D View this record in MEDLINE/PubMed
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2014 Zhou et al 2014 Zhou et al
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Conceived and designed the experiments: JHZ WD. Performed the experiments: JHZ YFW YW. Analyzed the data: JHZ YFH. Contributed reagents/materials/analysis tools: XY LLC WWW TL. Wrote the paper: JHZ.
Competing Interests: The authors have declared that no competing interests exist.
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Snippet Cisplatin is commonly used in ovarian cancer chemotherapy, however, chemoresistance to cisplatin remains a great clinical challenge. Oncogenic transcriptional...
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StartPage e96989
SubjectTerms 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
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Title FOXM1 Modulates Cisplatin Sensitivity by Regulating EXO1 in Ovarian Cancer
URI https://www.ncbi.nlm.nih.gov/pubmed/24824601
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https://www.proquest.com/docview/1524817586
https://pubmed.ncbi.nlm.nih.gov/PMC4019642
https://doaj.org/article/6aa1baa3f4f140f28e080466f88a1a47
http://dx.doi.org/10.1371/journal.pone.0096989
Volume 9
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