miRNA-200c enhances radiosensitivity of esophageal cancer by cell cycle arrest and targeting P21.

Esophageal squamous cancer is one of the most fatal malignancies and often suffer recurrence after radiotherapy. Downregulation of miRNA-200c is associated with radiotolerance. We aim to investigate the role of miRNA-200c in radiosensitivity and develop a systemic treatment strategy for esophageal squamous cancer. Overexpression of miRNA-200c by transfection was determined by RT-PCR. Radiosensitizing effect of miRNA-200c on esophageal squamous cancer cells was determined by clonogenic assay and xenograft model. Cell cycle was analyzed by flow cytometry. The levels of Cyclin B1, cyclin D1, cyclin E1, CDK2, CDK4, Cdc2 and P21 protein expressions were detected by western blotting. The results of our study revealed that miRNA-200c enhanced the radiosensitivity significantly in esophageal squamous cancer cell line in vitro and in vivo. miRNA-200c induced G2/M and sub-G1 phase arrest and reduced S phase rate of the irradiated Eca-109 cells and downregulated expression levels of Cyclin B1, cdc2 and upregulated P21 expression level. Present results demonstrate that downregulation of miRNA-200c is associated with radiotolerance. miRNA-200c increases radiosensitivity by G2/M and sub-G1 phase arrest through modulating Cyclin B1, cdc2 and P21 expression levels.