MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-β/Smad2/STAT3/STAT5 pathway

Lung cancer is one of the primary causes of mortality worldwide and drug resistance is the key contributing factor which results in the failure of lung cancer chemotherapy. Previous studies have shown that microRNA (miR)-10a was involved in the reversal of cisplatin (DDP) resistance in numerous types of tumors; however, the underlying mechanism of action of this remains to be fully elucidated. In the present study, miR-10a silencing in human DDP-resistant lung cancer A549/DDP cells was demonstrated to improve DDP sensitivity, apoptosis, intracellular rhodamine-123 content as well as the expression and activity of caspase-3/8. In addition, miR-10a suppressed the cellular expression of P-glycoprotein, multi-drug resistance protein (MDR) 1, MDR-associated protein 1, RhoE, B cell lymphoma-2 and survivin in A549/DDP cells. Furthermore, miR-10a silencing inhibited the secretion of transforming growth factor (TGF)-beta, phosphorylation of Sma- and Mad-related protein (Smad)2, signal transducer and activator of transcription (STAT)3 and STAT5, the transcriptional activity of hypoxia-inducible factor and eukaryotic translation initiation factor 4E in human lung cancer A549/DDP cell line. These results therefore indicated that miR-10a may be a potential target for improving the effectiveness of lung cancer chemotherapy via regulation of the TGF-beta/Smad2/STAT3/STAT5 pathway.