title: microRNA-125b inhibits tube formation of blood vessels through translational suppression of VE-cadherin.
abstract: Angiogenesis is controlled positively or negatively by extrinsic and intrinsic molecular cues in endothelial cells (ECs); in the tumor microenvironment, the action of positive regulators exceeds that of negative regulators. Thus, overinduction of negative regulators may inhibit tumor angiogenesis. MicroRNAs (miRNAs or miRs) are endogenous short noncoding RNAs regulating gene expression either through translational inhibition or destabilization of target mRNA. Here, we show that miR-125b expression is transiently induced in ECs on stimulation with vascular endothelial growth factor or by ischemia. miR-125b inhibits translation of vascular endothelial (VE)-cadherin mRNA and in vitro tube formation by ECs. Injection of miR-125b into the tumor inhibited VE-cadherin expression by ECs and induced nonfunctional blood vessel formation, resulting in inhibition of tumor growth. It has been suggested that pro-angiogenic signals in ECs also upregulate anti-angiogenic molecules simultaneously via negative feedback. Because miR-125b induction in ECs is transient after pro-angiogenic stimulation, prolonged overexpression of miR-125b could result in blood vessel regression. Thus, miR-125b may be useful in cancer therapy by causing the collapse of the lumen of ECs.
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Muramatsu
authors.forename: H
authors.initials: H
authors.lastname: Kidoya
authors.forename: H
authors.initials: H
authors.lastname: Naito
authors.forename: S
authors.initials: S
authors.lastname: Sakimoto
authors.forename: N
authors.initials: N
authors.lastname: Takakura
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006614:Hindlimb / Q000098:blood supply; D061307:Human Umbilical Vein Endothelial Cells / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D035683:MicroRNAs; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000099152:Cadherin 5; C527468:Mirn125 microRNA, mouse; C467480:vascular endothelial growth factor A, mouse