Radiosensitivity varies among patients with non-small cell lung cancer (NSCLC). In this work, we aimed to investigate microRNAs associated with this heterogeneity among individuals. We selected miR-1246 from the microRNAs that were revealed by microarray experiments to be differentially expressed between radioresistant and parental cell lines. Both intracellular and extracellular miR-1246 was found to be upregulated after irradiation in a time-dependent pattern, resulting in increased radioresistance of NSCLC cells. We found that mTOR was a direct target gene of miR-1246, which mediated miR-1246-induced autophagy activation. Yin Yang-1 (YY1) was demonstrated to be a new transcription factor that regulates miR-1246 and CDR1as was found to be a circular RNA that sequesters miR-1246, which was confirmed in NSCLC cells and clinical samples. Finally, combining these data with the results from The Cancer Genome Atlas (TCGA), we verified that miR-1246 could be used as a biomarker to predict NSCLC patients' radiosensitivity and prognosis. Overall, our study fully investigated the effect of miR-1246 on radiosensitivity and comprehensively investigated the potential of miR-1246 as a prognostic biomarker and radiotherapy sensitization target.
Keywords: CDR1as; YY1; autophagy; mTOR; miR-1246; radiosensitivity.
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