MiR-21 mediates the radiation resistance of glioblastoma cells by regulating PDCD4 and hMSH2

作者: Teng-fei Chao , Hui-hua Xiong , Wei Liu , Yang Chen , Jia-xuan Zhang

DOI: 10.1007/S11596-013-1153-4

关键词: Cancer researchFlow cytometryCell cultureMolecular biologymicroRNAApoptosisRadiation sensitivityCell cycleTransfectionGene knockdownBiology

摘要: The purpose of this study was to investigate the molecular mechanism by which miR-21 and its target genes mediate radiation resistance glioblastoma cells. Real-time PCR employed detect expression in normal brain tissues, tissues cell lines (A172, T98G U87MG). cells were transfected with anti-miR-21 oligonucleotides, or plasmids containing PDCD4 hMSH2 (PDCD4-pcDNA3 hMSH2-pcDNA3). survival curve obtained sensitivity radiation. Cell apoptosis measured using Caspase-3/7 kit cycle flow cytometry. Western blotting performed miR-21-inhibiting results showed that conversely associated sensitivity. Over-expression resulted resistance, while knockdown led higher glioblastma After knockdown, significantly increased G(2) phase arrest more significant. In addition, endogenous hMSH2, contributed findings suggested may against via hMSH2. MiR-21 be used as potential targets for clinical radiotherapy sensitization future.

参考文章(22)
Yu Zhang, Shiying Yu, Liang Zhuang, Zu’an Zheng, Tengfei Chao, Qiang Fu, Caveolin-1 is involved in radiation-induced ERBB2 nuclear transport in breast cancer cells Journal of Huazhong University of Science and Technology [Medical Sciences]. ,vol. 32, pp. 888- 892 ,(2012) , 10.1007/S11596-012-1053-Z
Lee P Lim, Margaret E Glasner, Soraya Yekta, Christopher B Burge, David P Bartel, Vertebrate microRNA genes. Science. ,vol. 299, pp. 1540- 1540 ,(2003) , 10.1126/SCIENCE.1080372
Yu Zhang, Tengfei Chao, Ran Li, Wei Liu, Yang Chen, Xingqi Yan, Yanhua Gong, Bin Yin, Wei Liu, Boqing Qiang, Jizhong Zhao, Jiangang Yuan, Xiaozhong Peng, MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a. Journal of Molecular Medicine. ,vol. 87, pp. 43- 51 ,(2009) , 10.1007/S00109-008-0403-6
Zhiwei Zhong, Zhuo Dong, Lihua Yang, Zhaohui Gong, miR-21 induces cell cycle at S phase and modulates cell proliferation by down-regulating hMSH2 in lung cancer Journal of Cancer Research and Clinical Oncology. ,vol. 138, pp. 1781- 1788 ,(2012) , 10.1007/S00432-012-1287-Y
Lindsey E. Becker Buscaglia, Yong Li, Apoptosis and the target genes of microRNA-21. Chinese Journal of Cancer. ,vol. 30, pp. 371- 380 ,(2011) , 10.5732/CJC.011.10132
Lynette M Moore, Wei Zhang, Targeting miR-21 in glioma: a small RNA with big potential. Expert Opinion on Therapeutic Targets. ,vol. 14, pp. 1247- 1257 ,(2010) , 10.1517/14728222.2010.527334
Shuguang Zhang, Yi Wan, Tianhong Pan, Xiaoyan Gu, Chunfa Qian, Guan Sun, Lihua Sun, Yangzheng Xiang, Zhimin Wang, Lei Shi, MicroRNA-21 Inhibitor Sensitizes Human Glioblastoma U251 Stem Cells to Chemotherapeutic Drug Temozolomide Journal of Molecular Neuroscience. ,vol. 47, pp. 346- 356 ,(2012) , 10.1007/S12031-012-9759-8
Michael R. Horsman, Lothar Bohm, Geoffrey P. Margison, Luka Milas, Jean-Francois Rosier, Geza Safrany, Edgar Selzer, Marcel Verheij, Jolyon H. Hendry, Tumor radiosensitizers--current status of development of various approaches: report of an International Atomic Energy Agency meeting. International Journal of Radiation Oncology Biology Physics. ,vol. 64, pp. 551- 561 ,(2006) , 10.1016/J.IJROBP.2005.09.032
Yu Ren, Xuan Zhou, Mei Mei, Xu-Bo Yuan, Lei Han, Guang-Xiu Wang, Zhi-Fan Jia, Peng Xu, Pei-Yu Pu, Chun-Sheng Kang, MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol BMC Cancer. ,vol. 10, pp. 27- 27 ,(2010) , 10.1186/1471-2407-10-27
Yang Chen, Wei Liu, Tengfei Chao, Yu Zhang, Xingqi Yan, Yanhua Gong, Boqin Qiang, Jiangang Yuan, Maosheng Sun, Xiaozhong Peng, MicroRNA-21 down-regulates the expression of tumor suppressor PDCD4 in human glioblastoma cell T98G Cancer Letters. ,vol. 272, pp. 197- 205 ,(2008) , 10.1016/J.CANLET.2008.06.034