Regulation of TGF-β-mediated endothelial-mesenchymal transition by microRNA-27.
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.
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.
Hiroshi I
HI
Suzuki
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Akihiro
A
Katsura
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Hajime
H
Mihira
Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Masafumi
M
Horie
Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Akira
A
Saito
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kohei
K
Miyazono
D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; D016212:Transforming Growth Factor beta
Elk1; EndMT; TGF-β; microRNA; α-SMA