Open Access

MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway

  • Authors:
    • Zehang Zhuang
    • Fengchun Hu
    • Jing Hu
    • Cheng Wang
    • Jinsong Hou
    • Zhiqiang Yu
    • Tony T. Wang
    • Xiqiang Liu
    • Hongzhang Huang
  • View Affiliations

  • Published online on: August 11, 2017     https://doi.org/10.3892/or.2017.5899
  • Pages: 2051-2061
  • Copyright: © Zhuang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Accumulating data suggest that microRNAs (miRNAs) play a pivotal role in the regulation of tumor cell sensitivity to chemotherapeutic agents. Although the roles of a few miRNAs have been identified in cisplatin resistance, little is known in regards to the concerted contribution of miRNA‑mediated biological networks. In the present study, we demonstrated that microRNA-218 (miR-218) was significantly upregulated in cisplatin-resistant oral cancer cells. The results of cell viability and apoptosis assay showed that ectopic expression of miR-218 induced cell survival and resistance to cisplatin, whereas suppression of miR-218 caused apoptosis and enhanced sensitivity to cisplatin. Moreover, we identified PPP2R5A as a new direct target of miR-218 by using the dual luciferase reporter assay. Overexpression of miR-218 led to inhibition of PPP2R5A expression, whereas knockdown of miR-218 increased PPP2R5A levels. Introduction of PPP2R5A abrogated miR‑218-mediated cell survival and drug resistance. Furthermore, suppression of miR-218 or PPP2R5A significantly promoted or reduced cisplatin-induced apoptosis, respectively. Finally, PPP2R5A overexpression or β-catenin knockdown inhibited miR-218-mediated Wnt activation and partially restored cell sensitivity. Our data revealed a molecular link between miR-218 and PPP2R5A/Wnt signaling and implicates miR-218 as a potential target for oral cancer therapy.
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October-2017
Volume 38 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhuang Z, Hu F, Hu J, Wang C, Hou J, Yu Z, Wang TT, Liu X and Huang H: MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway. Oncol Rep 38: 2051-2061, 2017
APA
Zhuang, Z., Hu, F., Hu, J., Wang, C., Hou, J., Yu, Z. ... Huang, H. (2017). MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway. Oncology Reports, 38, 2051-2061. https://doi.org/10.3892/or.2017.5899
MLA
Zhuang, Z., Hu, F., Hu, J., Wang, C., Hou, J., Yu, Z., Wang, T. T., Liu, X., Huang, H."MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway". Oncology Reports 38.4 (2017): 2051-2061.
Chicago
Zhuang, Z., Hu, F., Hu, J., Wang, C., Hou, J., Yu, Z., Wang, T. T., Liu, X., Huang, H."MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway". Oncology Reports 38, no. 4 (2017): 2051-2061. https://doi.org/10.3892/or.2017.5899