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Int J Biol Sci 2011; 7(3):347-363. doi:10.7150/ijbs.7.347

Research Paper

MiR-21 plays an Important Role in Radiation Induced Carcinogenesis in BALB/c Mice by Directly Targeting the Tumor Suppressor Gene Big-h3

Cong Liu1#, Bailong Li1#, Ying Cheng1#, Jing Lin1, Jun Hao2, Shuyu Zhang3, R.E.J. Mitchel4, Ding Sun1, Jin Ni1, Luqian Zhao1, Fu Gao1✉, Jianming Cai1✉

1. Department of Radiation Medicine, Second Military Medical University, Xiangyin Road, Shanghai 200433, PR China;
2. Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Xiangyin Road, Shanghai 200433, PR China;
3. School of Radiation Medicine and Public Health, Medical College of Soochow University, Suzhou 215123, China;
4. Radiation Protection Research and Instrumentation Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, ON, K0J 1J0, Canada.
# These authors contributed equally to this work.

Abstract

Dysregulation of certain microRNAs (miRNAs) in cancer can promote tumorigenesis, metastasis and invasion. However, the functions and targets of only a few mammalian miRNAs are known. In particular, the miRNAs that participates in radiation induced carcinogenesis and the miRNAs that target the tumor suppressor gene Big-h3 remain undefined. Here in this study, using a radiation induced thymic lymphoma model in BALB/c mice, we found that the tumor suppressor gene Big-h3 is down-regulated and miR-21 is up-regulated in radiation induced thymic lymphoma tissue samples. We also found inverse correlations between Big-h3 protein and miR-21 expression level among different tissue samples. Furthermore, our data indicated that miR-21 could directly target Big-h3 in a 3′UTR dependent manner. Finally, we found that miR-21 could be induced by TGFβ, and miR-21 has both positive and negative effects in regulating TGFβ signaling. We conclude that miR-21 participates in radiation induced carcinogenesis and it regulates TGFβ signaling.

Keywords: Radiation-induced carcinogenesis, Radiation induced thymic lymphoma, MicroRNA, miR-21, Big-h3, TGFβ.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Liu C, Li B, Cheng Y, Lin J, Hao J, Zhang S, Mitchel REJ, Sun D, Ni J, Zhao L, Gao F, Cai J. MiR-21 plays an Important Role in Radiation Induced Carcinogenesis in BALB/c Mice by Directly Targeting the Tumor Suppressor Gene Big-h3. Int J Biol Sci 2011; 7(3):347-363. doi:10.7150/ijbs.7.347. Available from http://www.ijbs.com/v07p0347.htm