title: MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1.
abstract: Ovarian cancer is commonly treated with cisplatin and paclitaxel combination chemotherapy; however, ovarian cancer cells often develop resistance to these drugs. Increasingly, microRNAs (miRNAs) including miR-873 have been implicated in drug resistance in many cancers, but the role of miR-873 in ovarian cancer remains unknown. MTT cell viability assays revealed that the sensitivities of ovarian cancer lines to cisplatin and paclitaxel increased following transfection with miR-873 (P < 0.05). After predicting the miR-873 binding region in the 3'-untranslated region of ABCB1, dual-luciferase reporter assay confirmed this prediction. RT-PCR and Western blotting revealed that MDR1 expression was significantly downregulated after transfection with miR-873 and upregulated after transfection with anti-miR-873 at both mRNA and protein levels compared to negative controls (P < 0.05). Experiments in a mouse xenograft model confirmed that intratumoral administration of miR-873 could enhance the efficacy of cisplatin in inhibiting tumor growth in ovarian cancer in vivo (P < 0.05). ABCB1 overexpression reduced sensitivities of ovarian cancer lines OVCAR3 and A2780 to cisplatin and paclitaxel, which can be reversed by miR-873 mimic transfection (P < 0.05). In summary, we demonstrated that overexpression of miR-873 increased the sensitivity of ovarian cancer cells to cisplatin and paclitaxel by targeting MDR1 expression. Our findings suggest that combination therapies with chemotherapy agents and miR-873 may suppress drug resistance in ovarian cancer.
authors: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110013, People's Republic of China.
authors: Di-di
authors: DD
authors: Wu
authors: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110013, People's Republic of China.
authors: Xue-Song
authors: XS
authors: Li
authors: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110013, People's Republic of China.
authors: Xiao-Na
authors: XN
authors: Meng
authors: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110013, People's Republic of China.
authors: Jing
authors: J
authors: Yan
authors: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110013, People's Republic of China. zongzhi_999@163.com.
authors: Zhi-Hong
authors: ZH
authors: Zong
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000493:pharmacokinetics / Q000627:therapeutic use; D003536:Cystadenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D011897:Random Allocation; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; C000598459:MIRN873 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017239:Paclitaxel; D002945:Cisplatin
keywords: ABCB1; Cisplatin; Drug resistance; Ovarian cancer; miR-873