Downregulation of exosomal miR-1273a increases cisplatin resistance of non-small cell lung cancer by upregulating the expression of syndecan binding protein

Resistance to platinum-based drugs, such as cisplatin (CDDP), has been one of the major factors adversely affecting the clinical prognosis of patients with advanced non-small cell lung cancer (NSCLC). While it has been demonstrated that dysregulation of microRNAs (miRNAs) may contribute to cisplatin resistance in NSCLC, the underlying mechanisms remain largely unclear. In the present study, the effect of exosomal miR-1273a on cisplatin sensitivity of NSCLC was investigated. Microarray analysis was conducted to analyze the miRNA expression profiles in exosomes isolated from A549 cells treated with or without CDDP, and miR-1273a was found to be the most prominently downregulated miRNA in CDDP-treated exosomes. Overexpression of miR-1273a significantly increased the cytotoxicity of CDDP and induced apoptosis in A549 cells. Syndecan binding protein (SDCBP) was predicted to be a direct target of miR-1273a by bioinformatics and was found to be downregulated by miR-1273a in A549 cells. Furthermore, decreased plasma exosomal miR-1273a and increased plasma SDCBP levels were found to be associated with worse therapeutic outcomes of patients with advanced NSCLC receiving platinum-based chemotherapy. These findings suggest that miR-1273a is closely associated with the development of cisplatin resistance and may serve as a potential prognostic biomarker and therapeutic target for NSCLC.