LncRNA NORAD/miR-202-5p regulates the drug resistance of A549/DDP to cisplatin by targeting P-gp.

Abstract

In this study, we established the DDP-resistant NSCLC cell line A549/DDP to detect the effect of NORAD on cisplatin resistance of A549/DDP cells. NORAD was highly expressed in A549/DDP cells compared with A549 cells. The MTT data showed that knockdown of NORAD enhanced the inhibition rate of cisplatin on the A549/DDP cells and decreased IC50 value. The colony formation and MTT assay suggested that cisplatin inhibited cell proliferation, and knockdown of NORAD enhanced the inhibitory effect of cisplatin on A549/DDP cells. Besides, we found that NORAD silence reduced the P-gp expression but not BCRP, LRP and MRP. Moreover, NORAD could directly bind to miR-202-5p, and ABCB1 was a target of miR-202-5p. The MTT assay found that miR-202-5p inhibitor reversed the effects of NORAD silence on cisplatin resistance of A549/DDP cells. Then, the Western blot data showed that knockdown of NORAD reduced P-gp expression, and miR-202-5p inhibitor enhanced P-gp expression. ABCB1 overexpression reversed the inhibitory effect of NORAD knockdown on A549/DDP cells. Moreover, NORAD could directly bind to miR-202-5p, and ABCB1 was a target of miR-202-5p. Inhibition of miR-202-5p and overexpression of ABCB1 eliminated the effects of NORAD silence on cisplatin resistance of A549/DDP cells. Overexpression of miR-202-5p suppressed P-gp expression in A549/DDP cells. Collectively, our data showed that NORAD could enhance the DDP resistance of A549/DDP cells and potentially increased P-gp expression by sponging the miR-202-5p.