Department of Radiotherapy, Weifang People's Hospital, Shandong, China.
Endoscopy Center, Weifang People's Hospital, Shandong, China.
Free Radic Res. 2020 Oct;54(10):756-764. doi: 10.1080/10715762.2020.1841900. Epub 2020 Nov 5.
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.
非小细胞肺癌(NSCLC)是最常见的肺癌类型。放射抵抗是 NSCLC 放射治疗的一个重大障碍。长链非编码 RNA LINC00473 已被发现影响几种恶性肿瘤的放射治疗。本研究旨在探讨 LINC00473 调节 NSCLC 细胞放射敏感性的潜在作用和机制。通过实时定量 PCR 测量 LINC00473 和 miR-513a-3p 的水平。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)和不同剂量辐射暴露下的集落存活测定评估 LINC00473 对 NSCLC 细胞活力和细胞存活的影响。荧光素酶报告基因测定用于研究 LINC00473 与 miR-513a-3p 之间的相关性。本研究表明,与放射敏感患者相比,放射抵抗 NSCLC 患者的相对 LINC00473 表达上调,miR-513a-3p 表达下调。上调的 LINC00473 表达与放射治疗后 NSCLC 患者的预后不良相关。辐射以剂量和时间依赖的方式导致 LINC00473 表达增加。在不同剂量的辐射下,LINC00473 的敲低显着促进了 NSCLC 细胞的放射敏感性。LINC00473 是 miR-513a-3p 的海绵,并负调控 miR-513a-3p 的表达。总之,抑制 miR-513a-3p 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,为提高 NSCLC 患者放射治疗的敏感性提供了有前途的治疗靶点。