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

Pei Ning Yu, Ming D. Yan, Hung-Cheng Lai, Rui Lan Huang, Yu Ching Chou, Wen Chi Lin, Li Tzu Yeh, Ya W. Lin

研究成果: 雜誌貢獻文章同行評審

85 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)542-551
頁數10
期刊International Journal of Cancer
134
發行號3
DOIs
出版狀態已發佈 - 2013
對外發佈

ASJC Scopus subject areas

  • 癌症研究
  • 腫瘤科

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