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Oncol Rep. 2017 Oct;38(4):2051-2061. doi: 10.3892/or.2017.5899. Epub 2017 Aug 11.

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

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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.


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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