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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2010;3(3):211-222
Original Article
MicroRNA-21 is involved in ionizing radiation-promoted liver carcinogenesis
Yun Zhu, Xiaoyan Yu, Hanjiang Fu, Hongyan Wang, Ping Wang, Xiaofei Zheng, Ya Wang
Department of Radiation Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, GA
30322, USA; Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, 130021,
China; Beijing Institute of Radiation Medicine, Beijing 100850, China.
Received July 9, 2010; accepted July 28, 2010; available online July 31, 2010
Abstract: It has been known for decades that ionizing radiation (IR) promotes carcinogenesis and high-linear energy transfer (LET) IR
has a higher risk than low-LET IR for carcinogenesis; however, the mechanism remains unclear. MicroRNAs (miRNAs) have a critical
effect on carcinogenesis through post-transcriptional modification. In this study, our purpose is to explore whether miRNAs are involved
in IR- (especially high-LET IR) promoted liver carcinogenesis. We showed here that among several hundred miRNAs, miR-21 was the
only one that increased 6 folds in high-LET IR-promoted mouse liver tumors when compared with that in the non-irradiated liver
tissues. We also showed that miR-21 was up-regulated in human or mouse hepatocytes after exposure to IR, as well as in liver
tissues derived from whole body irradiated mice. The increased level of miR-21 was more significant in high-LET irradiated cells or
liver tissues. After the non-irradiated, low-LET or high-LET irradiated human hepatocytes were over-expressed with miR-21, these cells
became tumorigenesis in nude mice. The tumors derived from high-LET-irradiated-cells were largest, and accompanied by more
significant changes in the miR-21-targets: PTEN and RECK. In addition, we showed that IR-induced up-regulation of miR-21 depended
on the up-regulation/activation of AP-1 (at an earlier time, within 2 h) and the ErbB/Stat3 pathway (at a later time, more than 2 h), which
was also IR dose dependent. Taken together, we conclude that IR-induced up-regulation of miR-21 plays an important role in IR
(especially high-LET IR)-promoted liver carcinogenesis. (IJCEM1007002).
Keywords: microRNA, miR-21, ionizing radiation, carcinogenesis
Full Text PDF
Address all correspondence to:
Ya Wang, Ph.D.
Department of Radiation Oncology
Emory University School of Medicine
1365 Clifton Rd., Suite C5090
Atlanta, GA 30322
Tel: (404) 778-1832
Fax: (404) 778-1750
Email: yawang@radonc.emory.org
Original Article
MicroRNA-21 is involved in ionizing radiation-promoted liver carcinogenesis
Yun Zhu, Xiaoyan Yu, Hanjiang Fu, Hongyan Wang, Ping Wang, Xiaofei Zheng, Ya Wang
Department of Radiation Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, GA
30322, USA; Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, 130021,
China; Beijing Institute of Radiation Medicine, Beijing 100850, China.
Received July 9, 2010; accepted July 28, 2010; available online July 31, 2010
Abstract: It has been known for decades that ionizing radiation (IR) promotes carcinogenesis and high-linear energy transfer (LET) IR
has a higher risk than low-LET IR for carcinogenesis; however, the mechanism remains unclear. MicroRNAs (miRNAs) have a critical
effect on carcinogenesis through post-transcriptional modification. In this study, our purpose is to explore whether miRNAs are involved
in IR- (especially high-LET IR) promoted liver carcinogenesis. We showed here that among several hundred miRNAs, miR-21 was the
only one that increased 6 folds in high-LET IR-promoted mouse liver tumors when compared with that in the non-irradiated liver
tissues. We also showed that miR-21 was up-regulated in human or mouse hepatocytes after exposure to IR, as well as in liver
tissues derived from whole body irradiated mice. The increased level of miR-21 was more significant in high-LET irradiated cells or
liver tissues. After the non-irradiated, low-LET or high-LET irradiated human hepatocytes were over-expressed with miR-21, these cells
became tumorigenesis in nude mice. The tumors derived from high-LET-irradiated-cells were largest, and accompanied by more
significant changes in the miR-21-targets: PTEN and RECK. In addition, we showed that IR-induced up-regulation of miR-21 depended
on the up-regulation/activation of AP-1 (at an earlier time, within 2 h) and the ErbB/Stat3 pathway (at a later time, more than 2 h), which
was also IR dose dependent. Taken together, we conclude that IR-induced up-regulation of miR-21 plays an important role in IR
(especially high-LET IR)-promoted liver carcinogenesis. (IJCEM1007002).
Keywords: microRNA, miR-21, ionizing radiation, carcinogenesis
Full Text PDF
Address all correspondence to:
Ya Wang, Ph.D.
Department of Radiation Oncology
Emory University School of Medicine
1365 Clifton Rd., Suite C5090
Atlanta, GA 30322
Tel: (404) 778-1832
Fax: (404) 778-1750
Email: yawang@radonc.emory.org
