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

Cancer Gene Therapy volume 30, pages 1249–1259 (2023)Cite this article

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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.

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Fig. 1: LINC00173 was upregulated in radioresistant NPC tissues and cell lines.
Fig. 2: LINC00173 induced radioresistance of NPC in vitro.
Fig. 3: LINC00173 induced radioresistance of NPC in vivo.
Fig. 4: LINC00173 interacted directly with CHK2.
Fig. 5: LINC00173 inhibited apoptosis via ATM/CHK2/P53 signalling pathway in NPC.
Fig. 6: Model of LINC00173 inducing radioresistance via inhibiting CHK2/P53 signalling pathway in NPC.

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Data availability

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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Acknowledgements

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].

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Author notes

  1. These authors contributed equally: Jingjing Miao, Boyu Chen, Yunyun Xiao.

  2. These authors jointly supervised this work: Lin Wang, Haiqiang Mai, Chong Zhao.

Authors and Affiliations

  1. Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, 510060, China

    Jingjing Miao, Xiao Xiao, Shunzhen Lu, Xuguang Wang, Qiuyan Chen, Yanqun Xiang, Xiang Guo, Lin Wang, Haiqiang Mai & Chong Zhao

  2. Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, 510060, China

    Boyu Chen, Yunyun Xiao, Ying Ouyang & Xiangfu Chen

  3. Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, 510060, China

    Runda Huang, Lu Zhang & Xiaowu Deng

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Contributions

JM, BC, YX, LW, HM, and CZ conceived, designed, and directed the study. JM, BC, and YX performed the in vitro and in vivo experiments and data analyses. RH, XX, SL, LZ, and XW performed the clinical data analyses. YO performed the ISH and TENEL experiments. XC performed part of the WB experiments. JM, BC, YX, LW, HM, and CZ wrote and critically reviewed the manuscript. All authors read and approved the final manuscript. The order of the co–first authors was assigned based on the relative contributions of these individuals.

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Correspondence to Lin Wang, Haiqiang Mai or Chong Zhao.

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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

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