MiR-21 mediates the radiation resistance of glioblastoma cells by regulating PDCD4 and hMSH2.
10.1007/s11596-013-1153-4
- Author:
Teng-fei CHAO
1
;
Hui-hua XIONG
;
Wei LIU
;
Yang CHEN
;
Jia-xuan ZHANG
Author Information
1. Cancer Centre, Huazhong University of Science and Technology, Wuhan, 430030, China, turnface@126.com.
- Publication Type:Journal Article
- MeSH:
Apoptosis Regulatory Proteins;
genetics;
Cell Line, Tumor;
Glioblastoma;
genetics;
Humans;
MicroRNAs;
genetics;
MutS Homolog 2 Protein;
genetics;
RNA-Binding Proteins;
genetics;
Radiation Tolerance;
genetics
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2013;33(4):525-529
- CountryChina
- Language:English
-
Abstract:
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 G(2) phase arrest was more significant. In addition, miR-21 knockdown increased the expression of endogenous PDCD4 and hMSH2, which contributed to the apoptosis and G(2) 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.
