Novel Epigenetic CREB-miR-630 Signaling Axis Regulates Radiosensitivity in Colorectal Cancer

Abstract

<div><p>Background</p><p>miR-630 has been reported to be a modulator of several cancers, but the mechanism by which is it influences radioresistance remains unknown. We aimed to identify the molecular function of miR-630 and its regulatory mechanism in colorectal cancer (CRC) cell lines.</p><p>Methodology</p><p>Overexpression and loss-of-function analyses of miR-630 were performed in CRC cell lines by measuring their levels of growth and apoptosis after ionic radiation (IR). Target genes were detected via a dual-luciferase assay and Western blot. Chromatin immunoprecipitation assay was carried out to identify the transcription factor regulating miR-630, and a demethylation experiment was also conducted.</p><p>Results</p><p>miR-630 expression was found to be positively correlated with radiosensitivity in CRC cell lines (<i>p</i><0.05). After IR treatment, miR-630 induced apoptosis in cells; however, the opposite was observed when miR-630 was downregulated (<i>p</i><0.05). BCL2L2 and TP53RK were identified as the target genes of miR-630, and the function of miR-630 was found to depend on these two genes (<i>p</i><0.05). In addition, evidence showed that CREB regulates the level of miR-630, and demethylation can elevate miR-630 levels (<i>p</i><0.05).</p><p>Conclusion</p><p>CREB–miR-630–BCL2L2 and TP53RK comprise a novel signaling cascade regulating radiosensitivity in CRC cell lines by inducing cell apoptosis and death.</p></div