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

Authors

  • Pei-Ning Yu,

    1. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China
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  • Ming-De Yan,

    1. Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China
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  • Hung-Cheng Lai,

    1. Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
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  • Rui-Lan Huang,

    1. Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
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  • Yu-Ching Chou,

    1. School of Public Health, National Defense Medical Center, Taipei, Taiwan, Republic of China
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  • Wen-Chi Lin,

    1. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China
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  • Li-Tzu Yeh,

    1. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China
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  • Ya-Wen Lin

    Corresponding author
    1. Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China
    2. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China
    • Correspondence to: Ya-Wen Lin, PhD, Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, No.161, Section 6, Min-Chuan East Road, Taipei 114, Taiwan, Republic of China, Fax: +886-2-87917654, E-mail: ndmc.yawen@msa.hinet.net or lyw@ndmctsgh.edu.tw

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  • Conflict of interest: Nothing to report

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.

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