The purpose of this study was to investigate the molecular mechanism by which miR-21 and its target genes mediate radiation resistance of glioblastoma cells.Real-time PCR was employed to detect miR-21 expression in normal brain tissues,glioblastoma tissues and glioblastoma cell lines (A172,T98G and U87MG).T98G cells were transfected with anti-miR-21 oligonucleotides,or plasmids containing PDCD4 or hMSH2 (PDCD4-pcDNA3 and hMSH2-pcDNA3).The survival curve was obtained to investigate the sensitivity of T98G cells to radiation.Cell apoptosis was measured by using the Caspase-3/7 kit and cell cycle by flow cytometry.Western blotting was performed to detect the expression of hMSH2 and PDCD4 in miR-21-inhibiting T98G cells.The results showed that miR-21 expression in glioblastoma cells and tissues was conversely associated with the radiation sensitivity.Over-expression of miR-21 resulted in radiation resistance,while knockdown of miR-21 led to higher sensitivity of glioblastma cells to radiation.After miR-21 knockdown,the apoptosis of T98G cells was significantly increased and the G2 phase arrest was more significant.In addition,miR-21 knockdown increased the expression of endogenous PDCD4 and hMSH2,which contributed to the apoptosis and G2 arrest of T98G cells.The findings suggested that miR-21 may mediate the resistance of glioblastoma cells against radiation via its target genes PDCD4 and hMSH2.MiR-21 and its target genes may be used as potential molecular targets for clinical radiotherapy sensitization in the future.
