Department of Radiation Medicine, Second Military Medical University, Xiangyin Road, Shanghai 200433, PR China.
Int J Biol Sci. 2011 Apr 1;7(3):347-63. doi: 10.7150/ijbs.7.347.
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.
某些 microRNAs（miRNAs）在癌症中的失调可促进肿瘤发生、转移和侵袭。然而，只有少数哺乳动物 miRNAs 的功能和靶标是已知的。特别是，参与辐射诱导致癌的 miRNAs 和靶向肿瘤抑制基因 Big-h3 的 miRNAs 仍然未被定义。在本研究中，我们使用 BALB/c 小鼠的辐射诱导胸腺淋巴瘤模型，发现辐射诱导的胸腺淋巴瘤组织样本中肿瘤抑制基因 Big-h3 下调，miR-21 上调。我们还发现不同组织样本中 Big-h3 蛋白和 miR-21 表达水平之间存在负相关。此外，我们的数据表明 miR-21 可以通过 3'UTR 依赖性方式直接靶向 Big-h3。最后，我们发现 miR-21 可以被 TGFβ诱导，并且 miR-21 在调节 TGFβ信号中具有正反两方面的作用。我们得出结论，miR-21 参与辐射诱导的致癌作用，并调节 TGFβ 信号。
