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 Apr 1;7(3):347-63. doi: 10.7150/ijbs.7.347.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Cell Proliferation / radiation effects
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Lymphoma / genetics*
  • Lymphoma / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / physiology*
  • Neoplasms, Radiation-Induced / genetics*
  • Neoplasms, Radiation-Induced / metabolism
  • Thymus Neoplasms / genetics*
  • Thymus Neoplasms / metabolism
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism

Substances

  • Extracellular Matrix Proteins
  • MIRN21 microRNA, mouse
  • MicroRNAs
  • Transforming Growth Factor beta
  • betaIG-H3 protein