Open Access

Gain-of-function microRNA screens identify miR-193a regulating proliferation and apoptosis in epithelial ovarian cancer cells

  • Authors:
    • Haruo Nakano
    • Yoji Yamada
    • Tatsuya Miyazawa
    • Tetsuo Yoshida
  • View Affiliations

  • Published online on: April 15, 2013     https://doi.org/10.3892/ijo.2013.1896
  • Pages: 1875-1882
  • Copyright: © Nakano et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

MicroRNAs (miRNAs) are a small class of non‑coding RNAs that negatively regulate gene expression, and are considered as new therapeutic targets for treating cancer. In this study, we performed a gain-of-function screen using miRNA mimic library (319 miRNA species) to identify those affecting cell proliferation in human epithelial ovarian cancer cells (A2780). We discovered a number of miRNAs that increased or decreased the cell viability of A2780 cells. Pro-proliferative and anti-proliferative miRNAs include oncogenic miR-372 and miR-373, and tumor suppressive miR-124a, miR-7, miR-192 and miR-193a, respectively. We found that overexpression of miR-124a, miR-192, miR-193a and miR‑193b inhibited BrdU incorporation in A2780 cells, indicating that these miRNAs affected the cell cycle. Overexpression of miR‑193a and miR-193b induced an activation of caspase 3/7, and resulted in apoptotic cell death in A2780 cells. A genome‑wide gene expression analysis with miR-193a-transfected A2780 cells led to identification of ARHGAP19, CCND1, ERBB4, KRAS and MCL1 as potential miR-193a targets. We demonstrated that miR-193a decreased the amount of MCL1 protein by binding 3'UTR of its mRNA. Our study suggests the potential of miRNA screens to discover miRNAs as therapeutic tools to treat ovarian cancer.
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June 2013
Volume 42 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Nakano H, Yamada Y, Miyazawa T and Yoshida T: Gain-of-function microRNA screens identify miR-193a regulating proliferation and apoptosis in epithelial ovarian cancer cells. Int J Oncol 42: 1875-1882, 2013
APA
Nakano, H., Yamada, Y., Miyazawa, T., & Yoshida, T. (2013). Gain-of-function microRNA screens identify miR-193a regulating proliferation and apoptosis in epithelial ovarian cancer cells. International Journal of Oncology, 42, 1875-1882. https://doi.org/10.3892/ijo.2013.1896
MLA
Nakano, H., Yamada, Y., Miyazawa, T., Yoshida, T."Gain-of-function microRNA screens identify miR-193a regulating proliferation and apoptosis in epithelial ovarian cancer cells". International Journal of Oncology 42.6 (2013): 1875-1882.
Chicago
Nakano, H., Yamada, Y., Miyazawa, T., Yoshida, T."Gain-of-function microRNA screens identify miR-193a regulating proliferation and apoptosis in epithelial ovarian cancer cells". International Journal of Oncology 42, no. 6 (2013): 1875-1882. https://doi.org/10.3892/ijo.2013.1896