Expression of miR-224-5p is associated with the original cisplatin resistance of ovarian papillary serous carcinoma

Zhao,Henan; Bi,Tie; Qu,Zhenyun; Jiang,Jiyong; Cui,Shiying; Wang,Yan

doi:10.3892/or.2014.3311

Expression of miR-224-5p is associated with the original cisplatin resistance of ovarian papillary serous carcinoma

Authors:
- Henan Zhao
- Tie Bi
- Zhenyun Qu
- Jiyong Jiang
- Shiying Cui
- Yan Wang
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Affiliations: Department of Pathophysiology, Dalian Medical University, Dalian, P.R. China, Obstetrics and Gynecology Hospital, Dalian, P.R. China, Department of Human Histology and Embryology, Dalian Medical University, Dalian, P.R. China, Laboratory Center, Second Affiliated Hospital of Dalian Medical University, Dalian, P.R. China
Published online on: July 7, 2014 https://doi.org/10.3892/or.2014.3311
Pages: 1003-1012

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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.

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