miR-134 regulates cisplatin resistance of human lung adenocarcinoma cells / 中国病理生理杂志

ABSTRACT

AIM:To investigate the roles of microRNA-134 (miR-134) in the cisplatin resistance of lung ade-nocarcinoma cells.METHODS:miRNA microarray was applied to compare the miRNA expression profile between A549/CDDP and A549 cells.Real-time PCR was used to confirm the expression of miR-134.miR-134 mimics and inhibitors were transfected into A549/CDDP and A549 cells, respectively.MTT assay was used to detect the sensitivity of lung cancer cells to cisplatin.Western blot was applied to test whether miR-134 regulated forkhead box protein M1 ( FOXM1 ) and multi-drug-associated protein 1 ( MRP1 ) expression.RESULTS: Based on the data of miRNA microarray, 13 miRNAs were found to be differentially expressed in A549/CDDP cells compared with A549 cells, among which miR-134 was the most significantly down-regulated one.Compared with control group, A549/CDDP cells transfected with miR-134 mimics showed greatly enhanced sensitivity to cisplatin as indicated by IC50 values (P<0.01).In contrast, suppression of the miR-134 level in the A549 cells resulted in a decreased sensitivity to cisplatin (P<0.01).FOXM1 siRNA down-regulated the pro-tein levels of FOXM1.A549/CDDP cells transfected with si-FOXM1 showed enhanced sensitivity to cisplatin (P<0.01). In addition, the result of Western blot showed that miR-134 repressed MRP1 protein expression.CONCLUSION: miR-134 effectively increases the sensitivity of lung adenocarcinoma cells to cisplatin, and this effect of miR-134 may be partly due to its regulation of FOXM1 and MRP1 expression.