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Upregulation of miR‐23a∼27a∼24 decreases transforming growth factor‐beta‐induced tumor‐suppressive activities in human hepatocellular carcinoma cells
Author(s) -
Huang Shenglin,
He Xianghuo,
Ding Jie,
Liang Linhui,
Zhao Yingjun,
Zhang Zhenfeng,
Yao Xiao,
Pan Zhimei,
Zhang Pingping,
Li Jinjun,
Wan Dafang,
Gu Jianren
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23580
Subject(s) - downregulation and upregulation , gene knockdown , microrna , cancer research , smad , transforming growth factor beta , transforming growth factor , hepatocellular carcinoma , biology , rna interference , cell growth , cancer , liver cancer , cell culture , microbiology and biotechnology , rna , gene , biochemistry , genetics
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.