title: Expression of miR-224-5p is associated with the original cisplatin resistance of ovarian papillary serous carcinoma.
abstract: Chemoresistance is a major challenge to successful chemotherapy of ovarian cancer, which represents the leading cause of mortality from gynecologic malignancies. We demonstrated that overexpression of miR-224-5p in ovarian cancer patients is associated with platinum-based chemoresistance using miRNA microarray analysis and quantitative real-time polymerase chain reaction (qRT-PCR) validation in vivo, as well as in 4 human ovarian cancer cell lines (C13/OV2008; A2780CP/A2780S) in vitro. In the present study, we aimed to clarify the role of miR-224-5p in regulating the chemoresistance of ovarian cancer. By using the sensitive miRNA transient transfection, we demonstrated expression and bioactivity of miR-224-5p in ovarian cancer cell lines. It is of note that enforced expression of miR-224-5p enhanced chemoresistance to cisplatin in ovarian cancer cells through apoptosis reversion. We predicted and identified the PRKCD gene as one of the targets of miR-224-5p in mediating the primary chemoresistance of ovarian cancer patients. We showed reciprocal expression of miR-224-5p and PRKCD by quantitative analysis in complete response and incomplete response patients in vivo, and 2 pairs of cisplatin resistance and sensitive cell lines in vitro, after either miR-224-5p overexpression or knockdown transfection. Additionally, miR-224-5p and PRKCD can serve as novel predictors and prognostic biomarkers for ovarian papillary serous carcinoma (OPSC) patient response to overall disease-specific survival. Our findings suggest that miR-224-5p may function as an oncogene and induce platinum resistance in OPSC at least in part by downregulating PRKCD, thereby providing a biomarker for predicting chemosensitivity to cisplatin in patients with ovarian cancer.
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, P.R. China.
authors.forename: Henan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Obstetrics and Gynecology Hospital, Dalian, P.R. China.
authors.forename: Tie
authors.initials: T
authors.lastname: Bi
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, P.R. China.
authors.forename: Zhenyun
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Obstetrics and Gynecology Hospital, Dalian, P.R. China.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Human Histology and Embryology, Dalian Medical University, Dalian, P.R. China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Cui
authors.affiliation: Laboratory Center, Second Affiliated Hospital of Dalian Medical University, Dalian, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: C546140:MIRN224 microRNA, human; D035683:MicroRNAs; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta; D002945:Cisplatin