Background: Glioma is the most prevalent malignant tumor in human central nervous systems. Recently, the\ndevelopment of resistance to radiotherapy in glioma patients markedly vitiates the therapy outcome. MiR-153-3p has\nbeen reported to be closely correlated with tumor progression, but its effect and molecular mechanism underlying\nradioresistance remains unclear in glioma.\nMethods: The expression of miR-153-3p was determined in radioresistant glioma clinical specimens as well as\nglioma cell lines exposed to irradiation (IR) using quantitative real-time PCR. Cell viability, proliferation and apoptosis\nwere then evaluated by MTT assay, colony formation assay, Flow cytometry analysis and caspase-3 activity assay in\nglioma cells (U87 and U251). Tumor forming was evaluated by nude mice model in vivo. TUNEL staining was used to\ndetect cell apoptosis in nude mice model. The target genes of miR-153-3p were predicted and validated using integrated\nbioinformatics analysis and a luciferase reporter assay.\nResults: Here, we found that miR-153-3p was down-regulated in radioresistant glioma clinical specimens as well as\nglioma cell lines (U87 and U251) exposed to IR. Enhanced expression of miR-153-3p promoted the radiosensitivity,\npromoted apoptosis and elevated caspase-3 activity in glioma cells in vitro, as well as the radiosensitivity in U251 cell\nmouse xenografs in vivo. Mechanically, B cell lymphoma-2 gene (BCL2) was identified as the direct and functional\ntarget of miR-153-3p. Moreover, restoration of BCL2 expression reversed miR-153-3p-induced increase of radiosensitivity,\napoptosis and caspase-3 activity in U251 cells in vitro. In addition, clinical data indicated that the expression of\nmiR-153-3p was significantly negatively associated with BCL2 in radioresistance of glioma samples.\nConclusions: Our findings suggest that miR-153-3p is a potential target to enhance the effect of radiosensitivity on\nglioma cells, thus representing a new potential therapeutic target for glioma.
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