MicroRNA miR-34b/c Enhances Cellular Radiosensitivity of Malignant Pleural Mesothelioma Cells

Background: We previously reported that epigenetic silencing of microRNA-34b1c (miR-34b/c) plays an important role in the pathogenesis of malignant pleural mesothelioma (MPM). We examined the impact of miR-34b/c restoration on the radiosensitivity of MPM cells. Materials and Methods: We established stable miR-34b/c and scramble transfectants of two MPM cell lines, H2052 and H28. We examined these transfectants by clonogenic survival assay, phosphorylated his-tone H2AX (gamma H2AX) foci assay, cell-cycle analysis, and western blotting. Results: The clonogenic survival assay revealed that miR-34b/c radiosensitized MPM cells. gamma H2AX foci assay showed that DNA double-strand break repair was delayed in miR-34b/c transfectants. The proportion of sub-G(1) phase cells was increased in miR-34b/c transfectants after irradiation. miR-34b/c inhibited expression of cyclin-D1, cyclin-dependent kinase 416, B-cell lymphoma-2 (BCL-2) and increased cleaved poly (ADP-ribose) polymerase (cPARP) and cleaved caspase-3 after irradiation. Conclusion: Our results indicate that miR-34b/c enhances radiosensitivity by promoting radiation-induced apoptosis and suggested that miR-34b/c might be a useful therapeutic molecule to enhance radiotherapy in MPM.