title: MiR-216b increases cisplatin sensitivity in ovarian cancer cells by targeting PARP1.
abstract: Cisplatin resistance hinders the efficacy of chemotherapy in ovarian cancer. MicroRNAs (miRs) have been implicated in drug resistance in anti-cancer chemotherapy. We compared the expression profiles of miRs between cisplatin-resistant and cisplatin-sensitive ovarian cancer cells, and found that miR-216b was significantly downregulated in cisplatin-resistant ovarian cancer cells. To investigate its molecular mechanism, we performed cell viability and apoptosis assays in cisplatin-resistant ovarian cells, and found that miR-216b reduced cell viability and promoted apoptosis. Although 4 potential targets were obtained through bioinformatics, only the mRNA level of poly(ADP-ribose) polymerase (PARP)-1 was significantly regulated by miR-216b. Disruption of the complementary binding sequence of miR-216b on the 3'-untranslated region (3'-UTR) of the PARP1 led to the loss of miR-216b targeting. Spearman's correlation coefficient of the levels of miR-216b and PARP1 mRNA from 51 human ovarian cancer specimens also showed a significantly negative correlation between them. Importantly, the improved cisplatin sensitivity induced by miR-216b was markedly reversed by PARP1 overexpression. Tumor formation assay in nude mice further provided an evidence on the suppressive role of miR-216b in tumor growth. Taken together, this study demonstrated that a new miRNA, miR-216b, was involved in cisplatin resistance in ovarian cancer, which could be regarded as a potential sensitizer in cisplatin chemotherapy.
authors.affiliation: Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, Jinan, China.|Department of Obstetrics and Gynecology, Liaocheng people's Hospital, Liaocheng, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Liaocheng people's Hospital, Liaocheng, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C575482:MIRN216 microRNA, human; D035683:MicroRNAs; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D002945:Cisplatin