title: MiR-197 induces Taxol resistance in human ovarian cancer cells by regulating NLK.
abstract: Chemotherapy is the preferred therapeutic approach for the therapy of advanced ovarian cancer, but 5-year survival rate remains low due to the development of drug resistance. Increasing evidence has documented that microRNAs (miRNAs) act important roles in drug resistance in a variety types of cancer. However, the roles of miRNA in regulating Taxol resistance in ovarian cancer and the detailed mechanism are less reported. We used Taqman probe stem loop real-time PCR to accurately measure the levels of miR-197 in normal ovarian cells, ovarian cancer cells, and Taxol-resistant ovarian cancer cells and found that miR-197 was significantly increased in Taxol-resistant ovarian cancer cells. Enforced expression of miR-197 can promote Taxol resistance, cell proliferation, and invasion of ovarian cancer cells. Meanwhile, repression of miR-197 in ovarian cancer cells can sensitize its response to Taxol and also induced attenuated cell proliferation and invasion ability. Furthermore, investigation of the detailed mechanism showed that the promotion of miR-197 on drug resistance in ovarian cancer cells was partially mediated by downregulating NLK, a negative regulator of WNT signaling pathway. Taken together, our work first demonstrated that miR-197 can confer drug resistance to Taxol, by regulating tumor suppressor, NLK expression in ovarian cancer cells.
authors.affiliation: Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China.
authors.forename: Dongling
authors.initials: D
authors.lastname: Zou
authors.affiliation: Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China.
authors.forename: Xingtao
authors.initials: X
authors.lastname: Long
authors.affiliation: Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China. qizhou9128@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C546085:MIRN197 microRNA, human; D035683:MicroRNAs; C470551:NLK protein, human; D017346:Protein Serine-Threonine Kinases; D017239:Paclitaxel
keywords: Drug resistance; NLK; Ovarian cancer; Taxol; miR-197
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