title: TGF-β-induced miR-21 negatively regulates the antiproliferative activity but has no effect on EMT of TGF-β in HaCaT cells.
abstract: The transforming growth factor-β (TGF-β) 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 ∼22 nucleotides that regulate gene expression at posttranscriptional levels. Increasing evidence points to the important role of miRNAs in TGF-β signaling. OncomicroRNA miR-21 has been established as a key regulator of mesenchymal phenotype transition induced by TGF-β. However, the effects of miR-21 on epithelial biology involved in TGF-β 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-β exposure in both growth inhibition and EMT models of HaCaT keratinocytes. To determine the potential roles of miR-21 in TGF-β-induced growth-arrest and EMT models, we showed that ectopic expression of miR-21 overcame TGF-β' 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-β-induced cytostatic program. Thus, our results suggest that miR-21 regulates the ability of epithelial cells to respond to TGF-β, with potential impact on epithelium homeostasis, wound-healing and tumorigenesis.
authors: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University, Chongqing 400038, China.
authors: Tao
authors: T
authors: Wang
authors: Lilong
authors: L
authors: Zhang
authors: Chunmeng
authors: C
authors: Shi
authors: Huiqin
authors: H
authors: Sun
authors: Junping
authors: J
authors: Wang
authors: Rong
authors: R
authors: Li
authors: Zhongmin
authors: Z
authors: Zou
authors: Xinze
authors: X
authors: Ran
authors: Yongping
authors: Y
authors: Su
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta