The aim of this study was to explore the role of TGF-β1/Smad4 signalling in the DNA damage-induced ionization radiation (IR) resistance of glioma cells. T98G cells were assigned to the IR group (treated with IR) or the Blank group (with no treatment). The IR-treated cells were also treated/transfected with the TGF-β receptor inhibitor SB431542, SUMO1-overexpressing plasmids (SUMO1 group), SUMO1-interfering plasmids (si-SUMO1 group) or negative control plasmids group. The wound-healing capacity, cell proliferation and cell apoptosis were evaluated by the scratch assay, flow cytometry and the CCK-8 assay, respectively, and protein interactions were investigated by coimmunoprecipitation and colocalization assays. IR-treated T98G cells had DNA damage, but the wound-healing capacity and cell apoptosis were not significantly suppressed. DNA damage also induced TGF-β1, Smad4, SUMO1, SUMO2/3 and Ubc9 expression. In IR-treated cells cultured with SB431542, the wound-healing capacity and proliferation were promoted. SUMO1 and Smad4 colocalized in the nucleus of T98G cells, and the IR-treated cells had a significantly higher expression of the SUMO1–Smad4 protein complex. Smad4 expression in the nucleus was significantly reduced in the si-SUMO1 group, but was markedly increased in the SUMO1 group; the SUMO1 group had significantly elevated apoptotic activity, whereas the si-SUMO1 group showed significantly suppressed apoptotic activity and the si-SUMO1+SB41542 group had the lowest levels of cell apoptosis. DNA damage may activate Smad4 SUMOylation and the SUMOylation of Smad4 participates in the activation of TGF-β/Smad4 signalling; therefore, enhanced Smad4 SUMOylation is critical for the damage-induced activation of IR resistance.
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