Long noncoding RNA LINC00173 induces radioresistance in nasopharyngeal carcinoma via inhibiting CHK2/P53 pathway.
Jingjing MiaoBoyu ChenYunyun XiaoRunda HuangXiao XiaoShunzhen LuLu ZhangXuguang WangYing OuyangXiangfu ChenQiuyan ChenYanqun XiangXiang GuoXiaowu DengLin WangHai-Qiang MaiChong ZhaoPublished in: Cancer gene therapy (2023)
Radiotherapy is the backbone of nasopharyngeal carcinoma (NPC), nearly 11-17% NPC patients suffered local relapse and 18-37% suffered distant metastasis mainly due to radioresistance. Therefore, the key of improving patients' survivals is to investigate the mechanism of radioresistance. In this study, we revealed that the expression level of long intergenic nonprotein coding RNA 173 (LINC00173) was significantly increased in the radioresistant NPC patients' tumour tissues compared with the radiosensitive patients by RNA-sequencing, which also predict poor prognosis in NPC. Overexpression of LINC00173 induced radioresistance of NPC cells in vitro and in vivo. Mechanistically, LINC00173 bound with checkpoint kinase 2 (CHK2) in nucleus, and impaired the irradiation-induced CHK2 phosphorylation, then suppressed the activation of P53 signalling pathway, which eventually inhibiting apoptosis and leading to radioresistance in NPC cells. In summary, LINC00173 decreases the occurrence of apoptosis through inhibiting the CHK2/P53 pathway, leads to NPC radioresistance and could be considered as a novel predictor and therapeutic target in NPC.
Keyphrases
- poor prognosis
- end stage renal disease
- long noncoding rna
- long non coding rna
- newly diagnosed
- chronic kidney disease
- ejection fraction
- cell proliferation
- peritoneal dialysis
- cell cycle arrest
- oxidative stress
- prognostic factors
- induced apoptosis
- single cell
- cell death
- radiation therapy
- early stage
- lymph node
- squamous cell carcinoma
- signaling pathway
- stress induced
- tyrosine kinase