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

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.