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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.

Author information

1
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, P.R. China.
2
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
3
Center for Infectious Diseases, SRI International, Harrisonburg, VA 22802, USA.

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.

PMID:
28849187
PMCID:
PMC5652945
DOI:
10.3892/or.2017.5899
[Indexed for MEDLINE]
Free PMC Article

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