MicroRNA-26b is known to be upregulated in high grade glioma and to play a crucial role in epithelial to mesenchymal transition (EMT). In this study, we evaluated the potential of targeting miRNA-26b to overcome the radioresistance of human malignant glioma cells. We also aimed to elucidate the mechanisms of radiosensitization by miR-26b.
U251 human glioma cells having activation of PI3K signaling due to deletion of PTEN were transfected with pre-miR-26b or control pre-miRNA. Ectopic overexpression of miR-26b attenuated the expression of p-AKT and enhanced the cytotoxicity of U251 cells by radiation. Overexpression of miR-26b prolonged radiation-induced gamma H2AX foci formation and attenuated the expression of p-DNA-PKcs. Increased expression of mature miR-26b also suppressed invasion, migration, vascular tube formation, and led to down-regulation of HIF-1alpha, VEGF and MMP-2 expression. In contrast, overexpression of miR-26b did not increased radiaton toxicity of normal human astrocytes.
Taken together, these findings suggest that miR-26b could be an attractive target for overcoming radioresistnace of human malignant glioma cells via unique modulation of the cancer pro-survival signaling and EMT.
Citation Format: David J. Lee, Yeo-Hyun Hwang, In Ah Kim. MicroRNA-26b potentiates cytotoxicity of malignant glioma cells by radiation. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A37.