Abstract

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Radioresistance is a significant obstacle in NSCLC radiotherapy. Long non-coding RNA LINC00473 has been found to impact the radiotherapy in several malignant tumours. This study aimed to investigate the underlying role and mechanism of LINC00473 in regulating radiosensitivity of NSCLC cells. The levels of LINC00473 and miR-513a-3p were measured by quantitative Real-Time PCR. The relationship of LINC00473 with overall survival was tested by the Kaplan-Meier method. The effects of LINC00473 on cell viability and cell survival were assessed by cell counting kit-8 (CCK-8) and colony survival assay in NSCLC cells exposed to different doses of radiation. A luciferase reporter assay was used to investigate the correlation between LINC00473 and miR-513a-3p. The present study showed that the relative LINC00473 expression was upregulated and miR-513a-3p expression was downregulated in radioresistant NSCLC patients compared with radiosensitive patients. And upregulated LINC00473 expression was associated with poor prognosis of NSCLC patients after radiotherapy. Radiation led to an increase in LINC00473 expression in a dose- and time-dependent manner. The knockdown of LINC00473 markedly promoted radiosensitivity in NSCLC cells under different doses of radiation. LINC00473 was a sponge of miR-513a-3p and negatively regulated the miR-513a-3p expression. In conclusion, the inhibition of miR-513a-3p markedly reversed the promoted effect of LINC00473 knockdown on cell radiosensitivity. LINC00473 inhibition enhances radiosensitivity of NSCLC by sponging miR-513a-3p, providing a promising therapeutic target to increase the sensitivity of radiotherapy in NSCLC patients.

摘要

非小细胞肺癌 (NSCLC) 是最常见的肺癌形式。放射抗性是NSCLC放疗的一个重要障碍。已发现长链非编码 RNA LINC00473 会影响多种恶性肿瘤的放射治疗。本研究旨在探讨LINC00473在调节NSCLC细胞放射敏感性中的潜在作用和机制。LINC00473 和 miR-513a-3p 的水平通过定量实时 PCR 测量。通过 Kaplan-Meier 方法测试 LINC00473 与总生存期的关系。通过细胞计数试剂盒-8 (CCK-8) 和暴露于不同辐射剂量的 NSCLC 细胞的集落存活测定，评估了 LINC00473 对细胞活力和细胞存活的影响。荧光素酶报告基因检测用于研究 LINC00473 和 miR-513a-3p 之间的相关性。本研究表明，与放射敏感的患者相比，放射抗性 NSCLC 患者的相对 LINC00473 表达上调，miR-513a-3p 表达下调。LINC00473表达上调与NSCLC患者放疗后预后不良有关。辐射导致 LINC00473 表达以剂量和时间依赖性方式增加。LINC00473 的敲低显着提高了 NSCLC 细胞在不同辐射剂量下的放射敏感性。LINC00473 是 miR-513a-3p 的海绵，负向调节 miR-513a-3p 的表达。总之，miR-513a-3p的抑制显着逆转了LINC00473敲低对细胞放射敏感性的促进作用。LINC00473 抑制通过海绵 miR-513a-3p 增强 NSCLC 的放射敏感性，