Anticancer Research. 2012 Nov;32(11):4871-5. [Link]
Maki Y, Asano H, Toyooka S, Soh J, Kubo T, Katsui K, Ueno T, Shien K, Muraoka T, Tanaka N, Yamamoto H, Tsukuda K, Kishimoto T, Kanazawa S, Miyoshi S.
Department of Thoracic Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. email@example.com.
We previously reported that epigenetic silencing of microRNA-34b/c (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 histone H2AX (Î³H2AX) foci assay, cell-cycle analysis, and western blotting.
The clonogenic survival assay revealed that miR-34b/c radiosensitized MPM cells. Î³H2AX 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 4/6, B-cell lymphoma-2 (BCL-2) and increased cleaved poly (ADP-ribose) polymerase (cPARP) and cleaved caspase-3 after irradiation.
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.