title: MiR-21 mediates the radiation resistance of glioblastoma cells by regulating PDCD4 and hMSH2.
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.
authors.affiliation: Cancer Centre, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Teng-Fei
authors.initials: TF
authors.lastname: Chao
authors.affiliation: Cancer Centre, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Xiong
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Bioinformatics, Bioinformatics Division/Center for Synthetic & Systems Biology, TNLIST, Tsinghua University, Beijing, 100084, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. 1109834322@qq.com.
authors.forename: Jia-Xuan
authors.initials: JX
authors.lastname: Zhang
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein
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