Free Radic Res. 2020 Oct 26:1-17. doi: 10.1080/10715762.2020.1841900. Online ahead of print.
AIM: 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 473 (LINC00473) has been found to impact the radiotherapy in several malignant tumors. This study aimed to investigate the underlying role and mechanism of LINC00473 in regulating radiosensitivity of NSCLC cells.
METHODS: 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.
RESULTS: 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. The inhibition of miR-513a-3p markedly reversed the promoted effect of LINC00473 knockdown on cell radiosensitivity.
CONCLUSION: 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.