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The role of miRNA in the direct and indirect effects of ionizing radiation
Authors:Jennifer S. Dickey  Franz J. Zemp  Olga A. Martin  Olga Kovalchuk
Affiliation:(1) Laboratory of Biochemistry, Division of Therapeutic Proteins, CDER, FDA, 29 Lincoln Drive, Bldg 29A, Room 2B-24, Bethesda, MD 20892, USA;(2) Department of Biological Sciences, University of Lethbridge, 4401 University Drive, Lethbridge, AB, T1K 3M4, Canada;(3) Present address: Department of Oncology, Tom Baker Cancer Center, Southern Alberta Cancer Research Institute, 3330 Hospital Drive N.W., Calgary, AB, T2N 4N1, Canada;(4) Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA;(5) Present address: Department of Radiation Oncology, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, VIC, 8006, Australia
Abstract:This review focuses on a number of recent studies that have examined changes in microRNA (miRNA) expression profiles in response to ionizing radiation and other forms of oxidative stress. In both murine and human cells and tissues, a number of miRNAs display significant alterations in expression levels in response to both direct and indirect radiation exposure. In terms of direct irradiation, or exposure to agents that induce oxidative stress, miRNA array analyses indicate that a number of miRNAs are up- and down-regulated and, in particular, the let-7 family of miRNAs may well be critical in the cellular response to oxidative stress. In bystander cells that are not directly irradiated, but close to, or share media with directly irradiated cells or tissues, the miRNA expression profiles are also altered, but are somewhat distinct from the directly irradiated cells. Based on the results of these numerous studies, as well as our own data presented here, we conclude that miRNA regulation is a critical step in the cellular response to radiation and oxidative stress and that future studies should elucidate the mechanisms through which this altered regulation affects cell metabolism.
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