Study on the effect of miR-29 on cisplatin resistance of ovarian cancer

• Main Authors: Pei-Ning Yu, 游珮寧
• Other Authors: Ya-Wen Lin
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/01396477385001012040

博士 === 國防醫學院 === 醫學科學研究所 === 102 === Epithelial ovarian cancer (EOC) is a common gynecologic malignancy and is one of the 10 most common causes of death by cancer in women. 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. However, the underlining mechanisms of cisplatine resistance in the subpopulation are still unknown. MicroRNAs (miRNAs), small noncoding RNAs, are involved in many biological events in cancer cells. In this study, we explored whether miRNAs are involved in cisplatin resistance of ovarian cancer cells. Our miRNA array and quantitative RT-PCR data showed that cisplatin-resistant cells expressed a lower level of miR-29a/b/c. Manipulation of 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 ERK1/2 and inactivation of GSK3. 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. In further investigation, we also found that the ovarian cancer patients with high expression of miR-29a had better overall survival rate. 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.