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Upregulation of miR-23a∼27a∼24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells

✍ Scribed by Shenglin Huang; Xianghuo He; Jie Ding; Linhui Liang; Yingjun Zhao; Zhenfeng Zhang; Xiao Yao; Zhimei Pan; Pingping Zhang; Jinjun Li; Dafang Wan; Jianren Gu


Publisher
John Wiley and Sons
Year
2008
Tongue
French
Weight
395 KB
Volume
123
Category
Article
ISSN
0020-7136

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✦ Synopsis


Abstract

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∼27a∼24, is induced 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 miR‐23a∼27a∼24 to TGF‐beta addition, indicating that this induction is dependent on Smad pathway. We also explore that miR‐23a∼27a∼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 findings suggest a novel, alternative mechanism through which TGF‐beta could induce specific miRNA expression to escape from tumor‐suppressive response in HCC cells. © 2008 Wiley‐Liss, Inc.