title: WSS25 inhibits Dicer, downregulating microRNA-210, which targets Ephrin-A3, to suppress human microvascular endothelial cell (HMEC-1) tube formation.
abstract: WSS25 is a sulfated polysaccharide that inhibits angiogenesis. However, the mechanism underlying the regulation of angiogenesis by WSS25 is not well understood. Using microRNA (miRNA) microarray analysis, a total of 25 miRNAs were found to be upregulated and 12 (including miR-210) downregulated by WSS25 in human microvascular endothelial cells (HMEC-1). Interestingly, Dicer, a key enzyme for miRNA biosynthesis, was downregulated by WSS25 in HMEC-1 cells. Further studies indicated that HMEC-1 cell tube formation and miR-210 expression were suppressed while Ephrin-A3 expression was enhanced by the silencing of Dicer. In contrast, HMEC-1 cell tube formation and miR-210 expression were induced while Ephrin-A3 expression was suppressed by Dicer overexpression. Moreover, miR-210 was downregulated while Ephrin-A3 was upregulated by WSS25 in HMEC-1 cells. HMEC-1 cell migration and tube formation were arrested, while Ephrin-A3 expression was augmented by anti-miR-210. In addition, HMEC-1 cell tube formation was significantly attenuated or augmented when Ephrin-A3 was overexpressed or silenced, respectively. Nevertheless, the tube formation blocked by WSS25 could be partially rescued by manipulation of Dicer, miR-210 and Ephrin-A3. These results suggest a new pathway whereby WSS25 inhibits angiogenesis via suppression of Dicer, leading to downregulation of miR-210 and upregulation of Ephrin-A3.
authors: Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors: Fei
authors: F
authors: Xiao
authors: Hong
authors: H
authors: Qiu
authors: Ling
authors: L
authors: Zhou
authors: Xiaokun
authors: X
authors: Shen
authors: Liping
authors: L
authors: Yang
authors: Kan
authors: K
authors: Ding
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002196:Capillaries / Q000166:cytology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D036384:Ephrin-A3 / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D005936:Glucans / Q000494:pharmacology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D043244:Ribonuclease III / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020533:Angiogenesis Inhibitors; D036384:Ephrin-A3; D005936:Glucans; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; C553930:WSS25 glucan; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases