MicroRNA-218 regulates cisplatin (DPP) chemosensitivity in non-small cell lung cancer by targeting RUNX2

Abstract

Downregulation of microRNA-218 (miR-218) is found in various human cancers, including non-small cell lung cancer (NSCLC). However, the involvement of chemosensitivity to cisplatin (DDP) and the underlying molecular mechanism remain unclear. In this study, we investigate whether miR-218 mediates NSCLC cell functions associated with chemoresistance. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect miR-218 expression in NSCLC cell lines A549/DDP and/or A549. The cell activity was measured by MTT assay. Cell cycle and cell apoptosis were detected by flow cytometry. Luciferase reporter assays and Western blots were used to validate runt-related transcription factor 2 (RUNX2) as a direct target gene of miR-218. miR-218 was significantly reduced in A549/DDP cells compared with parent A549 cells. Upregulation of miR-218 altered cell cycle-induced cell apoptosis and enhanced the sensitivity of A549/DDP cells to cisplatin. Mechanistically, RUNX2 was identified as a direct and functional target of miR-218, and RUNX2 executed the former on lung cancer chemoresistance. Our present study demonstrated for the first time that downregulation of miR-218 may contribute to the chemoresistance of NSCLC cells to cisplatin, which leads to upregulation of RUNX2. Uncovering the mechanism represents a novel approach to enhance the efficacy of chemotherapy during cancer treatment.