MiR-21 mediates the radiation resistance of glioblastoma cells by regulating PDCD4 and hMSH2 / 华中科技大学学报(医学)(英德文版)
Journal of Huazhong University of Science and Technology (Medical Sciences)
; (6): 525-529, 2013.
Article
em En
| WPRIM
| ID: wpr-251437
Biblioteca responsável:
WPRO
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.
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Índice:
WPRIM
Assunto principal:
Tolerância a Radiação
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Proteínas de Ligação a RNA
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Glioblastoma
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MicroRNAs
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Linhagem Celular Tumoral
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Proteína 2 Homóloga a MutS
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Proteínas Reguladoras de Apoptose
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Genética
Limite:
Humans
Idioma:
En
Revista:
Journal of Huazhong University of Science and Technology (Medical Sciences)
Ano de publicação:
2013
Tipo de documento:
Article