Suzuki Hiroshi I, Katsura Akihiro, Mihira Hajime, Horie Masafumi, Saito Akira, Miyazono Kohei
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St, 76-417, Cambridge, MA 02139, USA.
J Biochem. 2017 May 1;161(5):417-420. doi: 10.1093/jb/mvx017.
Multiple microRNAs (miRNAs) regulate epithelial-mesenchymal transition and endothelial-mesenchymal transition (EndMT). Here we report that microRNA-27b (miR-27b) positively regulates transforming growth factor-β (TGF-β)-induced EndMT of MS-1 mouse pancreatic microvascular endothelial cells. TGF-β induced miR-23b/24-1/27b expression, and inhibition of miR-27 suppressed TGF-β-mediated induction of mesenchymal genes. Genome-wide miRNA target analysis revealed that miR-27 targets Elk1, which acts as a competitive inhibitor of myocardin-related transcription factor-serum response factor signalling and as a myogenic repressor. miR-27b was also found to regulate several semaphorin receptors including Neuropilin 2, Plexin A2 and Plexin D1. These results suggest important roles of miR-27 in TGF-β-driven EndMT.
多种微小RNA（miRNA）可调节上皮-间充质转化和内皮-间充质转化（EndMT）。在此我们报告，微小RNA-27b（miR-27b）正向调节转化生长因子-β（TGF-β）诱导的MS-1小鼠胰腺微血管内皮细胞的EndMT。TGF-β诱导miR-23b/24-1/27b表达，而抑制miR-27可抑制TGF-β介导的间充质基因诱导。全基因组miRNA靶标分析显示，miR-27靶向Elk1，Elk1作为心肌素相关转录因子-血清反应因子信号传导的竞争性抑制剂及成肌抑制因子发挥作用。还发现miR-27b调节包括神经纤毛蛋白2、丛状蛋白A2和丛状蛋白D1在内的几种信号素受体。这些结果表明miR-27在TGF-β驱动的EndMT中起重要作用。
