The Critical Role Of MiR-449b In Tumor Cell Sensitivity To X-ray Radiation And Its Involved Mechanism

Objective:To investigate the effect of miR-449b on tumor cell sensitivity to X-ray radiation therapy and its involved mechanism.Methods:To study the role of NAC1 in tumor cell sensitivity to X-ray radiation,and the involved mechanism by which miR-449b contributes tumor cells sensitivity to X-ray radiation therapy.Cell biology,molecular biology,pharmacology and animal experiment methods were used in this study.Results:We demonstrate:1)miR-449b expression is positively correlated with X-ray radiation response in lung cancer tissues and different cancer cell lines;2)Ectopic expression of miR-449b with specific mimics significantly enhanced the cytotoxicity of X-ray therapy in tumor cells,as indicated by decreases in tumor cell viability andcolony formation,and increase in the amount of cleaved PARP;3)Bioinformatics prediction,luciferase reporter and rescue assay results showed that X-ray radiation therapy resistance reversal in response to miR-449b was mediated by eEF-2K which led to protein synthesis increase and ATP depletion,Conclusion:Protein synthesis increase and ATP depletion induced by miR-449b,which is mediated by eEF-2K,is involved in cellular sensitivity to X-ray radiation therapy.These findings demonstrate that the miR-449b is a novel regulator of ionizing radiation sensitivity in cancer cells,and maybe exploited as a potential new therapeutic target for reinforcement of radiotherapy efficacy.