Upregulation of miR-146a increases cisplatin sensitivity of the non-small cell lung cancer A549 cell line by targeting JNK-2

摘要

The aim of the present study was to investigate the effects of microRNA (miR-)146a on the cisplatin sensitivity of the non-small cell lung cancer (NSCLC) A549 cell line and study the underlying molecular mechanism. The differences in expression of miRNAs between A549 and A549/cisplatin (A549/DDP) cells were determined, and miR-146a was selected to study its effect on cisplatin sensitivity of A549/DDP cells. miR-146a mimic and inhibitor transient transfection systems were constructed using vectors, and A549/DDP cells were infected with miR-146a mimic and inhibitor to investigate growth, apoptosis and migration. The directed target of miR-146a was determined and the underlying molecular mechanism was validated in the present study. The results of the present study demonstrated that miR-146a was downregulated in NSCLC A549/DDP cells, compared with A549 cells. The overexpression of miR-146a induced apoptosis and inhibited the growth and invasion of A549/DDP cells, which resulted in increased cisplatin sensitivity in NSCLC cells. The JNK2 gene was determined as the direct target of miR-146a, and may be activated by the overexpression of miR-146a. Additionally, JNK2 activated the expression of p53 and inhibited B cell lymphoma 2. The upregulation of miR-146a increased cisplatin sensitivity of the A549 cell line by targeting JNK2, which may provide a novel method for treating NSCLC cisplatin resistance.