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.

放射治疗有助于治疗无法手术的非小细胞肺癌 (NSCLC)。研究表明，放疗会诱导内质网（ER）应激，从而诱导癌细胞凋亡和致敏。最近的一项研究表明，长链非编码 RNA (lncRNA) CASC2 与 NSCLC 细胞的恶性程度呈负相关。本研究调查了CASC2对NSCLC细胞放射敏感性和ER应激的影响和分子机制。CASC2 的过表达显着降低了细胞存活率并增加了细胞凋亡、PERK、磷酸化 eIF2α 和 CHOP 在受照射的人非小细胞肺癌细胞中的表达，而敲低 PERK 则逆转了这些影响。此外，CASC2 显着促进了 PERK mRNA 的稳定性，但对受照射的NSCLC细胞中PERK基因启动子的活性没有影响。引人注目的是，CASC2 对未照射的 NSCLC 细胞没有表现出明显的影响。该研究表明 lncRNA CASC2 增加了 PERK mRNA 的稳定性，从而触发了 PERK/eIF2α/CHOP ER 应激通路并促进了受照射的 NSCLC 细胞的放射敏感性或凋亡。本研究结果表明，CASC2可以作为有效的治疗靶点，提高放疗在NSCLC治疗中的疗效。