Upregulation of miR-23a∼27a∼24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells
Upregulation of miR-23a∼27a∼24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells
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DOI：
10.1002/ijc.23580
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发表时间：
2008-08-15
影响因子：
6.4
通讯作者：
Gu, Jianren
中科院分区：
文献类型：
--
作者：
Huang, Shenglin;He, Xianghuo;Gu, Jianren
转化生长因子-β (TGF-β) 在人类癌症中发挥着双重而复杂的作用。在本报告中，我们通过 miRNA 微阵列筛选观察到人类肝细胞癌 (HCC) 细胞中一组特定的 MicroRNA (miRNA) 响应 TGF-β 发生变化。 Huh-7 细胞中的 miRNA 簇（类似于 27a 和 24 的 miR-23a）在早期阶段被 TGF-β 诱导。通过RNA干扰敲低Smad4、Smad2或Smad3表达可减弱mik对TGF-β添加的反应，类似于23a、类似于27a、类似于24，表明这种诱导依赖于Smad途径。我们还探索了相似23a相似27a相似24的miR可以作为肝癌细胞的抗凋亡和促增殖因子。此外，与正常肝组织相比，该 miRNA 簇的表达在 HCC 组织中显着上调。这些发现提出了一种新颖的替代机制，通过该机制，TGF-β 可以诱导特定 miRNA 表达，以逃避 HCC 细胞的肿瘤抑制反应。 (c) 2008 年威利-利斯。公司
Transforming growth factor-beta (TGF-beta) plays a dual and complex role in human cancer. In this report, we observe a specific set of MicroRNAs (miRNAs) changed in response to TGF-beta in human hepatocellular carcinoma (HCC) cells by miRNA microarray screening. A cluster of miRNA, miR-23a similar to 27a similar to 24, is induce in an early stage by TGF-beta in Huh-7 cells. Knockdown of Smad4, Smad2 or Smad3 expression by RNA interference can attenuate the response of mik similar to 23a similar to 27a similar to 24 to TGF-beta addition, indicating that this induction is dependent on Smad pathway. We also explore that miR similar to 23a similar to 27a similar to 24 can function as an antiapoptotic and proliferation-promoting factor in liver cancer cells. In addition, expression of this miRNA cluster is found to be remarkably upregulated in HCC tissues versus normal liver tissues. These finaings suggest a novel, alternative mechanism through which TGF-beta could induce specific miRNA expression to escape from tumor-suppressive response in HCC cells. (c) 2008 Wiley-Liss. Inc.