TGF-β-induced miR-21 negatively regulates the antiproliferative activity but has no effect on EMT of TGF-β in HaCaT cells

The transforming growth factor-beta (TGF-beta) signaling pathway plays important roles in maintaining normal tissue homeostasis, and is tightly controlled by a network of biomolecules. MicroRNAs (miRNAs) are small noncoding RNAs of similar to 22 nucleotides that regulate gene expression at posttranscriptional levels. Increasing evidence points to the important role of miRNAs in TGF-beta signaling. OncomicroRNA miR-21 has been established as a key regulator of mesenchymal phenotype transition induced by TGF-beta. However, the effects of miR-21 on epithelial biology involved in TGF-beta signaling pathway such as cytostatic program and epithelial to mesenchymal transition (EMT) processes are unclear. Here we show that miR-21 is upregulated after TGF-beta exposure in both growth inhibition and EMT models of HaCaT keratinocytes. To determine the potential roles of miR-21 in TGF-beta-induced growth-arrest and EMT models, we showed that ectopic expression of miR-21 overcame TGF-beta growth-inhibitory effect and the knockdown of miR-21 potentialized this effect, but perturbation of miR-21 levels had little effect on EMT. Moreover, TGFBR2, PTEN, PDCD4, and TAp63 were identified as targets of miR-21 in HaCaT cells. And among them, TGFBR2, PTEN, and TAp63 were associated with TGF-beta-induced cytostatic program. Thus, our results suggest that miR-21 regulates the ability of epithelial cells to respond to TGF-beta, with potential impact on epithelium homeostasis, wound-healing and tumorigenesis. (C) 2011 Elsevier Ltd. All rights reserved.