Downregulation of miR‐29 contributes to cisplatin resistance of ovarian cancer cells

• Published in: International journal of cancer 2014-02, Vol.134 (3), p.542-551
• Main Authors: Yu, Pei‐Ning, Yan, Ming‐De, Lai, Hung‐Cheng, Huang, Rui‐Lan, Chou, Yu‐Ching, Lin, Wen‐Chi, Yeh, Li‐Tzu, Lin, Ya‐Wen
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cancer; Cell Line, Tumor; Chemotherapy; Cisplatin - therapeutic use; cisplatin resistance; COL1A1; Collagen Type I - physiology; Down-Regulation; Drug resistance; Drug Resistance, Neoplasm; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Medical research; Medical sciences; MicroRNAs; MicroRNAs - genetics; MicroRNAs - physiology; miR‐29; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.28399

Drug resistance is an obstacle to the treatment of ovarian cancer. Using a unique cell model, we have proven previously that a subpopulation of ovarian cancer cells is more resistant to cisplatin than are the original cells. MicroRNAs (miRNAs), small noncoding RNAs, are involved in many biological events in cancer cells. In our study, we explored whether miRNAs are involved in cisplatin resistance of ovarian cancer cells. Cisplatin‐resistant cells expressed a lower level of miR‐29a/b/c. Manipulation of microRNA‐29 (miR‐29) expression modulated cisplatin sensitivity of CP70, HeyC2, SKOV3 and A2780 ovarian cancer cells. Knockdown of miR‐29a/b/c increased the ability of cells to escape cisplatin‐induced cell death partly through upregulation of collagen type I alpha 1 (COL1A1) and increased the activation of extracellular signal‐regulated kinase 1/2 and inactivation of glycogen synthase kinase 3 beta. When combined with cisplatin treatment, knockdown of miR‐29 decreased the amount of the active form of caspase‐9 and caspase‐3. Ectopic expression of miR‐29 alone or in combination with cisplatin treatment efficaciously reduced the tumorigenicity of CP70 cells in vivo. Our data show that downregulation of miR‐29 increases cisplatin resistance in ovarian cancer cells. Taken together, these data suggest that overexpression of miR‐29 is a potential sensitizer to cisplatin treatment that may have therapeutic implications. What's new? MicroRNAs (miRNAs) are small, noncoding RNAs that are involved in a number of processes in cancer cells. In this study, the authors found that overexpression of miR‐29 can reduce drug resistance in ovarian cancer cells, in part through increased expression of collagen. Ectopic expression of miR‐29 alone or in combination with cisplatin treatment also reduced the tumorigenicity of CP70 cells in vivo. These data suggest that overexpression of miR‐29 may sensitize tumor cells to cisplatin treatment, and that this miRNA may therefore have therapeutic potential.