MicroRNA-146a regulates cisplatin-resistance of non-small cell lung cancer cells by targeting NF-κB pathway

Int J Clin Exp Pathol. 2017 Dec 1;10(12):11545-11553. eCollection 2017.


The aim of this study is to explore the influence of miR-146a on cisplatin resistance in non-small cell lung cancer (NSCLC) cells and the related molecular mechanism. The expression of miR-146a in NSCLC tumor samples and cell lines was measured by qRT-PCR. The DDP (cisplatin) cytotoxicity was detected by CCK-8 assay. The protein expressions of TRAF6, IRAK1, p50, p-p65, p65 in normal DDP-resistant cells were determined by western blot analysis. Luciferase reporter assay was used to investigate the relationship between miR-146a and NF-κB pathway activity. The expression of miR-146a in DDP-resistant NSCLC tumor samples was significantly lower than that in DDP-sensitive ones. Its expression in DDP-resistant cell lines was much lower as well. The protein levels of TRAF6, IRAK1 and p50 were up-regulated in A549/DDP and Calu-1/DDP cells compared to parental cells, and phosphorylation of p65 was also increased, indicating the activation of NF-κB signaling pathway. Furthermore, NF-κB activity was conversely related with miR-146a level in NSCLC. It was revealed that miR-146a expression in NSCLC was negatively correlated with activation of of NF-κB pathway. In conclusion, the study indicates that miR-146a regulates the DDP sensitivity by inhibiting NF-κB signaling pathway in NSCLC cells.

Keywords: DDP-resistance; MiR-146a; NF-κB; NSCLC.