Long noncoding RNA LINC00173 induces radioresistance in nasopharyngeal carcinoma via inhibiting CHK2/P53 pathway.

Abstract

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.

• Authors: Jingjing Miao, Boyu Chen, Yunyun Xiao, Runda Huang, Xiao Xiao, Shunzhen Lu, Lu Zhang, Xuguang Wang, Ying Ouyang, Xiangfu Chen, Qiuyan Chen, Yanqun Xiang, Xiang Guo, Xiaowu Deng, Lin Wang, Haiqiang Mai, Chong Zhao
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 30 Issue 9 Pg. 1249-1259 (09 2023) ISSN: 1476-5500 [Electronic] England
• PMID: 37258811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

Chemical References

• Checkpoint Kinase 2
• RNA, Long Noncoding
• Tumor Suppressor Protein p53
• CHEK2 protein, human
• TP53 protein, human
• long noncoding RNA LINC00173, human

Topics

• Humans
• Carcinoma (genetics)
• Cell Line, Tumor
• Checkpoint Kinase 2 (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Nasopharyngeal Carcinoma (genetics, radiotherapy, pathology)
• Nasopharyngeal Neoplasms (genetics, radiotherapy, pathology)
• Neoplasm Recurrence, Local (genetics)
• Radiation Tolerance (genetics)
• RNA, Long Noncoding (genetics)
• Signal Transduction (genetics)
• Tumor Suppressor Protein p53 (genetics, metabolism)