title: MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1.
abstract: The mechanism of cisplatin resistance in ovarian cancer is not clearly understood. In the present investigation, we found that the expression levels of miR-497 were reduced in chemotherapy-resistant ovarian cancer cells and tumor tissues due to hypermethylation of miR-497 promoter. Low miR-497 expression levels were associated with chemo-resistant phonotype of ovarian cancer. By analyzing the expression levels of miR-497, mTOR and p70S6K1 in a clinical gene-expression array dataset, we found that mTOR and p70S6K1, two proteins correlated to chemotherapy-resistance in multiple types of human cancers, were inversely correlated with miR-497 levels in ovarian cancer tissues. By using an orthotopic ovarian tumor model and a Tet-On inducible miR-497 expression system, our results demonstrated that overexpression of miR-497 sensitizes the resistant ovarian tumor to cisplatin treatment. Therefore, we suggest that miR-497 might be used as a therapeutic supplement to increase ovarian cancer treatment response to cisplatin.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Matenity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Urology and Pathology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
authors.forename: Guang-Bo
authors.initials: GB
authors.lastname: Fu
authors.affiliation: Department of Science and Technology, Radiation Oncology Department, Tianjin Medical University Cancer Hospital and Institute, Tianjin, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tao
authors.affiliation: Changzhou Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Changzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: OuYang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Matenity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Fanfei
authors.initials: F
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Reproductive Medicine, Cancer Center, Nanjing Medical University, China.|Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Matenity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wan
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019175:DNA Methylation; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D002945:Cisplatin
keywords: cisplatin resistance; mTOR; miR-497; ovarian cancer; p70S6K1