Long non-coding RNA XIST modulates cisplatin resistance by altering PDCD4 and Fas-Lexpressions in human nasopharyngeal carcinoma HNE1 cells .
10.12122/j.issn.1673-4254.2019.03.15
- Author:
Hao WANG
1
;
Wei LI
1
;
Guolin TAN
1
Author Information
1. Department of Otolaryngology-Head and Neck Surgery, Third Xiangya Hospital of Central South University, Changsha 410013, China.
- Publication Type:Journal Article
- Keywords:
Fas;
X inactive specific transcript;
cisplatin;
drug resistance;
nasopharyngeal carcinoma;
programmed cell death 4
- MeSH:
Antineoplastic Agents;
Apoptosis;
Apoptosis Regulatory Proteins;
Cell Line, Tumor;
Cell Proliferation;
Cisplatin;
Drug Resistance, Neoplasm;
Humans;
Nasopharyngeal Carcinoma;
RNA, Long Noncoding;
RNA-Binding Proteins;
fas Receptor
- From:
Journal of Southern Medical University
2019;39(3):357-363
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE: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.
METHODS: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.
RESULTS:The expression of XIST was significantly up-regulated in HNE1/DDP cells in comparison with HNE1 cells (0.57±0.06 0.1±0.02, < 0.05). Down-regulation of XIST significantly decreased while up-regulation of XIST obviously increased DDP resistance of HNE1/DDP cells ( < 0.05). Down-regulation of XIST significantly reduced the proliferation (6.17 ± 1.93 16.59 ± 4.86, < 0.05) and enhanced apoptosis [(18.04 ± 4.72)% (4.22 ± 1.65)%, < 0.05], while upregulating XIST enhanced the proliferation (25.40±7.21 13.16±3.95, < 0.05) and inhibited apoptosis [(2.82±0.88)% (6.46± 1.75)%, < 0.05] in HNE1/DDP cells. Down-regulation of XIST significantly increased the protein expressions of PDCD4 and Fas-L ( < 0.05) in HNE1/DDP cells, and up-regulation of XIST resulted in reverse changes in PDCD4 and Fas-L expressions ( < 0.05).
CONCLUSIONS: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.