lncRNA cytoskeleton regulator reduces non-small cell lung cancer radiosensitivity by downregulating miRNA-206 and activating prothymosin α

The present study aimed to explore the role of the long noncoding RNA cytoskeleton regulator (CYTOR) in non-small cell lung cancer (NSCLC) radiosensitivity by manipulating the microRNA (miR)-206/prothymosin α (PTMA) axis. First, 58 pairs of NSCLC and paracancerous tissues, normal human lung epithelial cells and NSCLC cells were collected to analyze CYTOR expression and the relation- ship between CYTOR and NSCLC prognosis. Subsequently, CYTOR expression in radioresistant cells was assessed. Radioresistant cells with low CYTOR expression and parental cells with high CYTOR expression were established. Functional assays were then performed to assess changes in cell radiosensitivity after irradiation treatment. Subsequently, the downstream mechanism of CYTOR was explored. The binding interactions between CYTOR and miR-206 and between miR-206 and PTMA were predicted and certified. Xenograft transplantation was applied to confirm the role of CYTOR in the radiosensitivity of NSCLC. CYTOR was overexpressed in NSCLC and was associated with poor prognosis. CYTOR was further upregulated in NSCLC cells with radioresistance. CYTOR knockdown enhanced the radiosensitivity of NSCLC cells, while overexpression of CYTOR led to the opposite result. Mechanistically, CYTOR specifically bound to miR-206 and silencing CYTOR promoted miR-206 to enhance the radiosensitivity of NSCLC cells. PTMA is a target of miR-206 and silencing CYTOR inhibited PTMA expression via miR-206, thus promoting radiosensitivity of NSCLC cells. CYTOR knockdown also enhanced NSCLC cell radiosensitivity in vivo. CYTOR was highly expressed in NSCLC, while silencing CYTOR potentiated NSCLC cell radiosensitivity by upregulating miR-206 and suppressing PTMA. The present study preliminarily revealed the role of CYTOR in radiotherapy sensitivity of NSCLC and provided a novel potential target for the clinical treatment of NSCLC.