Long non-coding RNA XIST modulates cisplatin resistance by altering PDCD4 and Fas-Lexpressions in human nasopharyngeal carcinoma HNE1 cells in vitro

Abstract

To explore the role of long non-coding RNA (lncRNA) X inactive specific transcript (XIST) in modulating cisplatin (DDP) resistance of human nasopharyngeal carcinoma cells and investigate the possible mechanism. Realtime PCR was performed to detect the expression of XIST in cisplatin-resistant human nasopharyngeal carcinoma cell line HNE1/DDP. The effects of up-regulation and down-regulation of XIST on DDP resistance, proliferation and apoptosis of HNE1/ DDP cells were assessed using MTT assay, EdU assay and flow cytometry. Western blotting was used to detect the changes in the expressions of programmed cell death 4 (PDCD4) and Fas ligand (Fas-L) proteins in the cells in response to up-regulation or down-regulation of XIST. The expression of XIST was significantly up-regulated in HNE1/DDP cells in comparison with HNE1 cells (0.57±0.06 vs 0.1±0.02, P < 0.05). Down-regulation of XIST significantly decreased while up-regulation of XIST obviously increased DDP resistance of HNE1/DDP cells (P < 0.05). Down-regulation of XIST significantly reduced the proliferation (6.17 ± 1.93 vs 16.59 ± 4.86, P < 0.05) and enhanced apoptosis [(18.04 ± 4.72)% vs (4.22 ± 1.65)%, P < 0.05], while upregulating XIST enhanced the proliferation (25.40±7.21 vs 13.16±3.95, P < 0.05) and inhibited apoptosis [(2.82±0.88)% vs (6.46± 1.75)%, P < 0.05] in HNE1/DDP cells. Down-regulation of XIST significantly increased the protein expressions of PDCD4 and Fas-L (P < 0.05) in HNE1/DDP cells, and up-regulation of XIST resulted in reverse changes in PDCD4 and Fas-L expressions (P < 0.05). XIST is up-regulated in HNE1/DDP cells, and down-regulation and up-regulation of XIST expression reduce and increase DDP resistance of the cells, respectively, possibly as a result of changes in the expressions of PDCD4 and Fas-L.