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.
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The RNA-seq data will be deposited in the National Centre for Biotechnology Information Sequence Read Archive database. Data described in the manuscript, code book, and analytic code will be made available upon request pending application and approval.
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This study was funded by National Natural Science Foundation of China for Young Scholars [No. 82202946 and No. 82003081] and National Natural Science Foundation of China [No. 82073330]; Guangdong Basic and Applied Basic Research Foundation [No. 2021A1515111112]; China Postdoctoral Science Foundation [No. 2021M703726]; Science and Technology Planning Project of Guangzhou City [No. 202102020106].
The authors declare no competing interests.
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Miao, J., Chen, B., Xiao, Y. et al. Long noncoding RNA LINC00173 induces radioresistance in nasopharyngeal carcinoma via inhibiting CHK2/P53 pathway. Cancer Gene Ther 30, 1249–1259 (2023). https://doi.org/10.1038/s41417-023-00634-x