MiR-21 is Continually Elevated Long-Term in the Brain after Exposure to Ionizing Radiation

被引:45
作者
Shi, Yan [1 ,2 ]
Zhang, Xiangming [1 ]
Tang, Xiaobing [1 ]
Wang, Ping [1 ]
Wang, Huichen [1 ]
Wang, Ya [1 ]
机构
[1] Emory Univ, Dept Radiat Oncol, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA
[2] Jilin Univ, Dept Expt Pharmacol & Toxicol, Sch Pharm, Changchun 130021, Peoples R China
基金
美国国家航空航天局;
关键词
NEGATIVE FEEDBACK; MOUSE HIPPOCAMPUS; DOWN-REGULATION; CANCER; MICRORNAS; CELLS; PTEN; EXPRESSION; PATHWAY; LIPOPOLYSACCHARIDE;
D O I
10.1667/RR2764.1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Shi, Y., Zhang, X., Tang, X., Wang, P., Wang, H. and Wang, Y. MiR-21 is Continually Elevated Long-Term in the Brain after Exposure to Ionizing Radiation. Radial. Res. 177, 124-128 (2012). Ionizing radiation stimulates miR-21 expression in different types of mammalian cells in culture. However, it remains unclear whether radiation could stimulate miR-21 expression in brain cells and tissue and, if so, how long the upregulation of miR-21 would be maintained after exposure to different types of radiation. To answer these questions, we examined the miR-21 levels in irradiated mouse hippocampal cells and brain tissue from mice at different times up to 1 year after whole-body exposure to 0.5 Gy of X rays [low linear energy transfer (LET)] or (56)Fe ions (high LET). The results showed that radiation stimulated miR-21 expression in mouse hippocampal cells and upregulation of EGFR, which is similar to that in human hepatocytes, as we reported previously. Interestingly, the miR-21 levels gradually increased within 1 year after irradiation, although there was no significant difference in the miR-21 low- and high-LET irradiated mice. The high expression of miR-21 in the brain was also associated with high expression of EGFR in irradiated mice; thus our data strongly support that EGFR and miR-21 are in a positive regulatory loop, because it is known that radiation stimulates miR-21 through the EGFR/Stat3 pathway and miR-21 activates the EGFR pathway. Since the brain is relatively resistant to radiation-induced histomorphological changes, our findings may provide a new way to explore radiation-induced pathological changes in the brain by investigating miR-21 and its multiple targets. (C) 2012 by Radiation Research Society
引用
收藏
页码:124 / 128
页数:5
相关论文
共 36 条
[1]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[2]   OncomiRs: the discovery and progress of microRNAs in cancers [J].
Cho, William C. S. .
MOLECULAR CANCER, 2007, 6 (1)
[3]  
CIAFRE S, 2005, BIOCHEM BIOPH RES CO, V334, P1381
[4]   miRNAs in the spotlight: Understanding cancer gene dependency [J].
Croce, Carlo M. .
NATURE MEDICINE, 2011, 17 (08) :935-936
[5]   Oncomirs - microRNAs with a role in cancer [J].
Esquela-Kerscher, A ;
Slack, FJ .
NATURE REVIEWS CANCER, 2006, 6 (04) :259-269
[6]   Localized CT-Guided Irradiation Inhibits Neurogenesis in Specific Regions of the Adult Mouse Brain [J].
Ford, E. C. ;
Achanta, P. ;
Purger, D. ;
Armour, M. ;
Reyes, J. ;
Fong, J. ;
Kleinberg, L. ;
Redmond, K. ;
Wong, J. ;
Jang, M. H. ;
Jun, H. ;
Song, H-J. ;
Quinones-Hinojosa, A. .
RADIATION RESEARCH, 2011, 175 (06) :774-783
[7]   Most mammalian mRNAs are conserved targets of microRNAs [J].
Friedman, Robin C. ;
Farh, Kyle Kai-How ;
Burge, Christopher B. ;
Bartel, David P. .
GENOME RESEARCH, 2009, 19 (01) :92-105
[8]   miR-21 gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism [J].
Fujita, Shuji ;
Ito, Taiji ;
Mizutani, Taketoshi ;
Minoguchi, Shigeru ;
Yamamichi, Nlobutake ;
Sakurai, Kouhei ;
Iba, Hlideo .
JOURNAL OF MOLECULAR BIOLOGY, 2008, 378 (03) :492-504
[9]   Radiation-induced regional cerebral blood volume (RCBV) changes in normal brain and low-grade astrocytomas: Quantification and time and dose-dependent occurrence [J].
Fuss, M ;
Wenz, F ;
Scholdei, R ;
Essig, M ;
Debus, J ;
Knopp, MV ;
Wannenmacher, M .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2000, 48 (01) :53-58
[10]   Up-regulation of miR-21 Mediates Resistance to Trastuzumab Therapy for Breast Cancer [J].
Gong, Chang ;
Yao, Yandan ;
Wang, Ying ;
Liu, Bodu ;
Wu, Wei ;
Chen, Jianing ;
Su, Fengxi ;
Yao, Herui ;
Song, Erwei .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (21) :19127-19137