Abstract 39: Mir-21 regulates TGF-β1-induced CAF formation through Smad7

Abstract

Abstract The TGF-β1, one of major cytokines secrected by tumor cells, not only promotes the growth of tumor cells themselves, but also transforms the adjacent stroma cells into cancer-associated fibroblast formation. However, the detail mechanism by which TGF-β1 induces CAF (cancer-associated fibroblast) formation is unveiled. In this study, the primary fibroblast from skin was successfully transformed into CAF in vitro. These TGF-β1-induced CAF cells significantly promoted the tumor growth in the A175 xenografted mice model. Moreover, the TGF-β1 stimulation not only increased the amount of miR-21, but also reduced the protein level of Smad 7 in primary fibroblast. The TGF-β1 accelerated the Drosha-mediated miR-21 maturation and the Smad 7 was identified to be a target of miR-21. Both the overexpression of miR-21 and knocking down of Smad 7 induced the CAF formation, which represented the TGF- β1 triggered phenotype in primary fibroblast. The Smad 7 physically associates with the Smad 2/3 and regulates the activation of Smad 2/3. The activation of Smad signaling globally changed the status of chromatin and triggered the reprogramming process and transformed the primary fibroblast into CAF. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 39. doi:1538-7445.AM2012-39