MiR-21 plays an important role in radiation induced carcinogenesis in BALB/c mice by directly targeting the tumor suppressor gene Big-h3.

MiR-21 plays an important role in radiation induced carcinogenesis in BALB/c mice by directly targeting the tumor suppressor gene Big-h3.
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MiR-21 通过直接靶向肿瘤抑制基因 Big-h3 在 BALB/c 小鼠辐射诱发的癌发生中发挥重要作用

DOI:
10.7150/ijbs.7.347
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发表时间:
2011-04-01
影响因子:
9.2
通讯作者:
Cai J
Cai J
中科院分区:
生物学2区
文献类型:
--
作者:
Liu C;Li B;Cheng Y;Lin J;Hao J;Zhang S;Mitchel RE;Sun D;Ni J;Zhao L;Gao F;Cai J

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肿瘤中某些微小RNAs(MiRNAs)的失调可促进肿瘤的发生、转移和侵袭。然而,只有少数哺乳动物miRNAs的功能和靶点是已知的。特别是,参与辐射致癌的miRNAs和针对肿瘤抑制基因Big-h3的miRNAs仍未确定。在本研究中,使用BALB/c小鼠辐射诱导的胸腺淋巴瘤模型,我们发现在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之间Big-h3蛋白和miR-21表达水平呈负相关。此外,我们的数据表明miR-21可以3‘非编码区依赖的方式直接靶向Big-h3。最后,我们发现转化生长因子β可以诱导miR-21,并且miR-21在调节转化生长因子β信号转导中既有积极的作用,也有消极的作用。结论:miR-21参与辐射致癌过程,调节转化生长因子β信号转导。
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.
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