Long noncoding RNA FAM201A involves in radioresistance of non-small-cell lung cancer by enhancing EGFR expression via miR-370.

Abstract

OBJECTIVE\nThe aberrant expression of long noncoding RNAs (lncRNAs) is involved in the molecular regulation of non-small cell lung cancer (NSCLC). This study aims to investigate the biological interaction of lnc-FAM201A and its downstream factors and their impacts on the radiotherapy response of NSCLC.\n\n\nPATIENTS AND METHODS\nQuantitative Polymerase Chain Reaction (qPCR) was used to determine the expression of FAM201A in NSCLC tissues. The Chi-square tests explored the association between FAM201A level and the poor clinicopathological characteristics (including radioresistance) of NSCLC. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate various prognostic factors for overall survival (OS). The effect of FAM201A on OS was tested by the log-rank test. A549/SK-MES-1 cell lines transfected with short hairpin RNA (shRNA) were used to verify the promoting effects of FAM201A on radiotherapy resistance in vitro and in vivo. Cell apoptosis (analyzed by flow cytometry), cell proliferation (determined by Cell Counting Kit-8), and mice xenograft models were performed to confirm the results. The downstream targets of FAM201A were predicted by bioinformatics tools. Additionally, the Dual-luciferase reporter assay, qPCR, and Western blotting were performed to confirm their interaction.\n\n\nRESULTS\nFAM201A was significantly upregulated in tissues obtained from NSCLC patients resistant to radiotherapy. Increased FAM201A expression was strongly associated with radioresistance and inferior survival in NSCLC, as demonstrated by clinical data. The silence of FAM201A could inhibit cell proliferation and further cell apoptosis of NSCLC cells under X-ray irradiation both in vitro and in vivo. Moreover, by competitively targeting miR-370, FAM201A elevated the epidermal growth factor receptor (EGFR) and the hypoxia-inducible factor 1alpha (HIF-1α) levels. After FAM201A knockdown, EGFR and HIF-1α were repressed with enhanced radiosensitivity.\n\n\nCONCLUSIONS\nThe interference of FAM201A impairs its suppression of miR-370, resulting in the upregulation of EGFR and HIF-1α and enhancement of radiosensitivity in NSCLC patients. Collectively, our results indicated that this regulatory axis might serve as a potential therapeutic target to increase the sensitivity of radiotherapy in NSCLC patients.