Plasma miRNA as Biomarkers for Assessment of Total-Body Radiation Exposure Dosimetry

被引:72
作者
Cui, Wanchang [1 ]
Ma, Jinfang [1 ]
Wang, Yulei [2 ]
Biswal, Shyam [1 ]
机构
[1] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA
[2] Life Technol, Genom Assays R&D, Foster City, CA USA
基金
美国国家卫生研究院;
关键词
CIRCULATING MICRORNAS; IONIZING-RADIATION; QUANTITATIVE DETECTION; SYSTEMIC RNAI; BLOOD; CANCER; MOUSE; DNA; EXPRESSION; VESICLES;
D O I
10.1371/journal.pone.0022988
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The risk of radiation exposure, due to accidental or malicious release of ionizing radiation, is a major public health concern. Biomarkers that can rapidly identify severely-irradiated individuals requiring prompt medical treatment in mass-casualty incidents are urgently needed. Stable blood or plasma-based biomarkers are attractive because of the ease for sample collection. We tested the hypothesis that plasma miRNA expression profiles can accurately reflect prior radiation exposure. We demonstrated using a murine model that plasma miRNA expression signatures could distinguish mice that received total body irradiation doses of 0.5 Gy, 2 Gy, and 10 Gy (at 6 h or 24 h post radiation) with accuracy, sensitivity, and specificity of above 90%. Taken together, these data demonstrate that plasma miRNA profiles can be highly predictive of different levels of radiation exposure. Thus, plasma-based biomarkers can be used to assess radiation exposure after mass-casualty incidents, and it may provide a valuable tool in developing and implementing effective countermeasures.
引用
收藏
页数:12
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共 51 条
[21]   Activated platelets release two types of membrane vesicles:: Microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and α-granules [J].
Heijnen, HFG ;
Schiel, AE ;
Fijnheer, R ;
Geuze, HJ ;
Sixma, JJ .
BLOOD, 1999, 94 (11) :3791-3799
[22]   The miR-34 family in cancer and apoptosis [J].
Hermeking, H. .
CELL DEATH AND DIFFERENTIATION, 2010, 17 (02) :193-199
[23]   Systemic RNAi in Caenorhabditis elegans [J].
Hunter, C. P. ;
Winston, W. M. ;
Molodowitch, C. ;
Feinberg, E. H. ;
Shih, J. ;
Sutherlin, M. ;
Wright, A. J. ;
Fitzgerald, M. C. .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 2006, 71 :95-100
[24]   Detection of microRNA Expression in Human Peripheral Blood Microvesicles [J].
Hunter, Melissa Piper ;
Ismail, Noura ;
Zhang, Xiaoli ;
Aguda, Baltazar D. ;
Lee, Eun Joo ;
Yu, Lianbo ;
Xiao, Tao ;
Schafer, Jeffrey ;
Lee, Mei-Ling Ting ;
Schmittgen, Thomas D. ;
Nana-Sinkam, S. Patrick ;
Jarjoura, David ;
Marsh, Clay B. .
PLOS ONE, 2008, 3 (11)
[25]   EXOSOME FORMATION DURING MATURATION OF MAMMALIAN AND AVIAN RETICULOCYTES - EVIDENCE THAT EXOSOME RELEASE IS A MAJOR ROUTE FOR EXTERNALIZATION OF OBSOLETE MEMBRANE-PROTEINS [J].
JOHNSTONE, RM ;
MATHEW, A ;
MASON, AB ;
TENG, K .
JOURNAL OF CELLULAR PHYSIOLOGY, 1991, 147 (01) :27-36
[26]   Secretory Mechanisms and Intercellular Transfer of MicroRNAs in Living Cells [J].
Kosaka, Nobuyoshi ;
Iguchi, Haruhisa ;
Yoshioka, Yusuke ;
Takeshita, Fumitaka ;
Matsuki, Yasushi ;
Ochiya, Takahiro .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (23) :17442-17452
[27]   New microRNAs from mouse and human [J].
Lagos-Quintana, M ;
Rauhut, R ;
Meyer, J ;
Borkhardt, A ;
Tuschl, T .
RNA, 2003, 9 (02) :175-179
[28]   Identification of tissue-specific microRNAs from mouse [J].
Lagos-Quintana, M ;
Rauhut, R ;
Yalcin, A ;
Meyer, J ;
Lendeckel, W ;
Tuschl, T .
CURRENT BIOLOGY, 2002, 12 (09) :735-739
[29]   Existence of a microRNA pathway in anucleate platelets [J].
Landry, Patricia ;
Plante, Isabelle ;
Ouellet, Dominique L. ;
Perron, Marjorie P. ;
Rousseau, Guy ;
Provost, Patrick .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2009, 16 (09) :961-U84
[30]   Differential stress induction of individual Alu loci: implications for transcription and retrotransposition [J].
Li, TH ;
Schmid, CW .
GENE, 2001, 276 (1-2) :135-141