title: Downregulation of miR-29 contributes to cisplatin resistance of ovarian cancer cells.
abstract: 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.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Pei-Ning
authors.initials: PN
authors.lastname: Yu
authors.forename: Ming-De
authors.initials: MD
authors.lastname: Yan
authors.forename: Hung-Cheng
authors.initials: HC
authors.lastname: Lai
authors.forename: Rui-Lan
authors.initials: RL
authors.lastname: Huang
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Chou
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Lin
authors.forename: Li-Tzu
authors.initials: LT
authors.lastname: Yeh
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D024042:Collagen Type I / Q000502:physiology; D000090602:Collagen Type I, alpha 1 Chain; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C000716127:COL1A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D002945:Cisplatin
keywords: COL1A1; cisplatin resistance; miR-29; ovarian cancer