Micro-RNA-21 regulates TGF-β-induced myofibroblast differentiation by targeting PDCD4 in tumor-stroma interaction
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Transforming growth factor-߱ (TGF-߱) induces stromal fibroblast-to-myofibroblast transdifferentiation in the tumor-stroma interactive microenvironment via modulation of multiple phenotypic and functional genes, which plays a critical role in tumor progression. Up to now, the involvement of micro-RNAs (miRNAs) and their roles in TGF-߱-induced myofibroblast differentiation in tumor-stroma interaction are unclear. Using quantitative real-time RT-PCR, we demonstrated that the expression of micro-RNA-21 (miR-21) was upregulated in activated fibroblasts after treatment with TGF-߱ or conditioned medium from cancer cells. To determine the potential roles of miR-21 in TGF-߱-mediated gene regulation during myofibroblast conversion, we showed that miR-21 expression was downregulated by miR-21 inhibitor and upregulated by miR-21 mimic. Interestingly, downregulation of miR-21 with the inhibitor effectively inhibited TGF-߱-induced myofibroblast differentiation while upregulation of miR-21 with a mimic significantly promoted myofibroblast differentiation. We further demonstrated that MiR-21 directly targeted and downregulated programmed cell death 4 (PDCD4) gene, which in turn acted as a negative regulator of several phenotypic and functional genes of myofibroblasts. Taken together, these results suggested that miR-21 participated in TGF-߱-induced myofibroblast transdifferentiation in cancer stroma by targeting PDCD4.
International Journal of Cancer
Copyright 2011 International Journal of Cancer. This is the pre-peer reviewed version of the following article: MicroRNA-21 regulates TGF-beta-induced myofibroblast differentiation by targeting PDCD4 in tumour-stroma interaction, Journal title, Vol128(8), 2011, pp.1783-1792, which has been published in final form at http://dx.doi.org/10.1002/ijc.25506.
Cancer Cell Biology