Microrna-129-5p-Mediated Inhibition Of Autophagy Enhanced The Radiosensitivity Of Human Colon Cancer Cells

The efficacy and outcome of radiotherapy in the treatment of colon cancer are much limited by radioresistance. Studies show microRNAs are involved in radioresistance in many cancers. In the present study, we aimed to explore the role of microRNA-129-5p in regulating radioresistance of colon cancer cells and its underlying mechanism. In the present study, we established a radioresistant colon cancer cell line. Compared with control group, miRNA-129-5p was significantly reduced whereas the autophagy was enhanced in radioresistant colon cancer cell line. Exotic expression of miRNA-129-5p was capable to inhibit beclin-1, a critical autophagy gene, and suppressed autophagy activity. Furthermore, we found beclin-1 was the direct target of miR-129-5p as evidenced by in silico analysis and luciferase reporter assay. In addition, overexpression of miRNA-129-5p inhibited cell growth and colony formation ability and promoted irradiation-induced apoptosis of radioresistant colon cancer cells. By contrast, overexpression of beclin-1 abolished the effects of miRNA-129-5p. In vivo, miRNA-129-5p sensitized xenograft tumor to irradiation. Taken together, the present study suggested that miRNA-129-5p significantly augmented the radiosensitivity of colon cancer cells through inhibiting beclin-1-mediated autophagy, hinting a promising new molecular target for the treatment of colon cancer.