Overexpression Of MiR-34a Delays Irradiation-induced H2AX Phosphorylation In Lung Cancer Cells

Objective:miR-34a is a member of the microRNAs that can be induced by ionizing radiation. In this study we paid close attention to the activation of H2AX and repair of DNA double strand breaks after irradiation in non-small cell lung cancer (NSCLC) cells and focus on the function of miR-34a in tumor radio-sensitivity. Methods:miR-34a mimics were transfected into NSCLC A549cells, and then irradiation-induced double strands breaks and DNA repair were analyzed by using micronucleus (MN) assay and single cell gel electrophoresis test in vitro. Western-blot was used to detect the dynamics of H2AX, yH2AX, and CCND1. At the same time, yH2AX foci were observed by immunofluorescence analysis. Cell cycle distributions and cell proliferation were detected by flow cytometry and CCK-8analysis, respectly. Results:After10Gy irradiation, miR-34a mimics-overexpressed A549cells displayed increased percentage of micronucleus positive cells. Restoration of miR-34a induced downregulation of CCND1protein and G0/G1arrest. In addition, overexpression of miR-34a delayed the phosphorylation of H2AX induced by irradiation. IR-induced H2AX-phosphorylation was delayed in G0/G1arrest A549cells as well as in miR-34a mimics overexpressed cells. Conclusion:Taken together, our data suggested that increased miR-34a expression in NSCLC A549cells could induce G0/G1arrest through CCND1down-regulation, which lead to delayed activation of H2AX and impaired DNA damage repair, finally increased radio-sensitivity of tumor A549cells. Objective:To investigate the expression pattern of RNA-binding protein R06O in tumor, and to identify the role of R06O in proliferation and radio-sensitivity of tumor cell.Methods:Tissue microarrays were used for immunohistochemical detecting of R06O protein in different types of malignant tumor tissues and their adjacent non-cancerous tissues. Cell proliferation and radio-sensitivity were detected by CCK-8assay. Results: The expression of R06O in malignant tumor tissues was significantly higher than that of their adjacent non-cancerous tissue controls, and the sub-cellular localizations of R06O were also changed in a series of tumor tissues. R06O in malignant tissues were significantly higher in nucleus than in cytoplasms of lung cancer, rectum cancer, breast cancer, and pancreatic cancer. There were obvious changes of R06O sub-cellular distribution in esophageal carcinoma and colon cancer, while no noticeable changes in gastric cancer, liver cancer, and renal cancer. Knock down R06O in lung cancer promote the cell proliferation and impaired IR-inuced tumor cell proliferation suppression. Conclusion: The expression of R06O in malignant tumor tissues was significantly increased. R06O played an important role in tumor cell proliferation and anti-radio therapy.