Abstract
Radiotherapy is instrumental in the treatment of inoperable non-small cell lung cancer (NSCLC). Studies have revealed that radiotherapy induces endoplasmic reticulum (ER) stress, which consequently induces apoptosis and sensitization of cancer cells. A recent study has revealed that long non-coding RNA (lncRNA) CASC2 is negatively correlated with the malignancy of NSCLC cells. The present study investigated the effects and molecular mechanisms of CASC2 on radiosensitivity and ER stress in NSCLC cells. The overexpression of CASC2 markedly decreased cell survival and increased apoptosis, expression of PERK, phosphorylated-eIF2α and CHOP in irradiated human NSCLC cells, whereas knocking down PERK reversed these effects. Moreover, CASC2 considerably promoted the stability of PERK mRNA, but had no effect on the activity of PERK gene promoter in irradiated NSCLC cells. Strikingly, CASC2 exhibited no apparent effect on non-irradiated NSCLC cells. This study demonstrated that lncRNA CASC2 increases the stability of PERK mRNA, which consequently triggers the PERK/eIF2α/CHOP ER stress pathway and promotes radiosensitivity or apoptosis in irradiated NSCLC cells. Results of the present study suggest that CASC2 can act as an effective therapeutic target to enhance the efficacy of radiotherapy in the treatment of NSCLC.
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The present study was supported by Natural Science Foundation of Hunan Province (grants #15A0106), Changsha, Hunan, People’s Republic of China.
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All authors participated in the design, interpretation of the studies and analysis of the data and review of the manuscript. YY, ZD and JK conducted the experiments, YY supplied critical reagents, ZD carried out the data collection, analysis and interpretation, wrote the manuscript. JK participated in the experiment process, data collection and analysis.
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Ding, Z., Kang, J. & Yang, Y. Long non-coding RNA CASC2 enhances irradiation-induced endoplasmic reticulum stress in NSCLC cells through PERK signaling. 3 Biotech 10, 449 (2020). https://doi.org/10.1007/s13205-020-02443-7
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DOI: https://doi.org/10.1007/s13205-020-02443-7