title: miR-100 resensitizes resistant epithelial ovarian cancer to cisplatin.
abstract: Epithelial ovarian cancer (EOC) is one of the malignant tumors that seriously affects women's health and chemotherapy resistance is an important reason for the poor prognosis. The present study was conducted to investigate whether microRNA-100 (miR-100) can be used to modulate the tolerance to cisplatin in EOC. Expression of miR-100 was compared between ovarian cancer cells tolerant and not tolerant to cisplatin. Mimic and antisense were used to study the roles and related mechanisms of miR-100 in cisplatin sensitivity in EOC. The alternation in the cisplatin sensitivity was investigated using grafted tumors derived from SKOV3/DDP cells with upregulated or downregulated miR-100 expression. miR-100 was lower in cisplatin resistant cell line SKOV3/DDP than in cisplatin sensitive cell line SKOV3. miR-100 might increase cisplatin sensitivity by inhibiting cell proliferation and conversion from G1 to S phase and increasing apoptosis. We showed that mTOR and PLK1 are targets of miR-100 and the cells were resensitized probably due to targeted downregulation of mTOR and PLK1 by miR-100. In vivo study with nude mice showed that tumors derived from miR-100 mimic-transfected cells were more sensitive to cisplatin and had reduced expression of mTOR and PLK1. miR-100 resensitizes resistant epithelial ovarian cancer to cisplatin probably by inhibiting cell proliferation, inducing apoptosis and arresting cell cycle and by targeted downregulation of mTOR and PLK1 expression.
authors.affiliation: Department of Obstetrics and Gynecology, Zhongshan People's Hospital, Zhongshan, Guangdong 528403, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Xiangpeng
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Sainan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Dongxian
authors.initials: D
authors.lastname: Peng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D000077216:Carcinoma, Ovarian Epithelial; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D002945:Cisplatin; D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D058570:TOR Serine-Threonine Kinases; D000097869:Polo-Like Kinase 1; C544266:MIRN100 microRNA, human; C546842:MTOR protein, human