Alterations of microRNAs in cisplatin-resistant human non-small cell lung cancer cells (A549/DDP).

ABSTRACT MicroRNAs (miRNAs) are a class of small, noncoding RNAs that posttranscriptionally regulate genes expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. Accumulating evidence suggests that miRNAs may play a role in chemoresistance and may be involved in the modulation of some drug resistance-related pathways in cancer cells. Here, the authors investigated the possible role of miRNAs in the development of drug resistance in lung cancer cell line. The results showed that 14 miRNAs were presented significantly (>2-fold), including up-regulation of 9 miRNAs and down-regulation of 5 miRNAs in A549/DDP cell line, compared with the parental A549 cell line. Up-regulation of miR-138 increased the sensitivity of A549/DDP cells to cisplatin in in vitro drug sensitivity assay, and increased apoptosis assessed by flow cytometry. The authors also found that excision repair cross-complementation group 1 (ERCC1) was negatively regulated by miR-138 and that down-regulation of ERCC1 at the protein level largely correlated with elevated levels of miR-138 in A549/DDP cells. Taken together, these findings suggest that miR-138 could play an important role in the development of cisplatin resistance in non-small cell lung cancer (NSCLC).