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Article 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 / Copyright

    Affiliations: Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, P.R. China, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Center for Infectious Diseases, SRI International, Harrisonburg, VA 22802, USA
    Copyright: © Zhuang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2051-2061
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    Published online on: August 11, 2017
       https://doi.org/10.3892/or.2017.5899
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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