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Heparin Impairs Angiogenesis through Inhibition of MicroRNA-10b

文献类型：期刊论文

作者Shen, Xiaokun1; Fang, Jianping1; Lv, Xiaofen1; Pei, Zhicao2; Wang, Ying1; Jiang, Songshan1,3,4; Ding, Kan1
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
出版日期2011-07-29
卷号286期号:30页码:26616-26627
ISSN号0021-9258
DOI10.1074/jbc.M111.224212
文献子类Article
英文摘要Heparin, which has been used as an anticoagulant drug for decades, inhibits angiogenesis, whereas thrombin promotes tumor-associated angiogenesis. However, the mechanisms underlying the regulation of angiogenesis by heparin and thrombin are not well understood. Here, we show that microRNA-10b (miR-10b) is down-regulated by heparin and up-regulated by thrombin in human microvascular endothelial cells (HMEC-1). Overexpression of miR-10b induces HMEC-1 cell migration, tube formation, and angiogenesis, and down-regulates homeobox D10 (HoxD10) expression via direct binding of miR-10b to the putative 3 ' UTR of HoxD10. In addition, HMEC-1 cell migration and tube formation are induced by HoxD10 knockdown, whereas angiogenesis is arrested when HoxD10 expression is increased after anti-miR-10b or heparin treatments. Furthermore, expression of miR-10b and its transcription factor Twist are up-regulated by thrombin, whereas HoxD10 expression is impaired by thrombin. Using quartz crystal microbalance analysis, we show that heparin binds to thrombin, thereby inhibiting thrombin-induced expression of Twist and miR-10b. However, the expression of miR-10b is not attenuated by heparin any more after thrombin expression is silenced by its siRNA. Interestingly, we find that heparin attenuates miR-10b expression and induces HoxD10 expression in vivo to inhibit angiogenesis and impair the growth of MDA-MB-231 tumor xenografts. These results provide insight into the molecular mechanism by which heparin and thrombin regulate angiogenesis.
WOS关键词MOLECULAR-WEIGHT HEPARINS ; CANCER-ASSOCIATED THROMBOSIS ; SULFATE PROTEOGLYCANS ; ENDOTHELIAL-CELLS ; VENOUS THROMBOEMBOLISM ; TUMOR ANGIOGENESIS ; TUBE FORMATION ; BREAST-CANCER ; GROWTH ; METASTASIS
资助项目National Natural Science Foundation of China[30770484] ; Chinese Academy of Sciences, China[00000000] ; Chinese Academy of Sciences, China ( to K. D.), and National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09301-001] ; Chinese Academy of Sciences, China ( to K. D.), and National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09501-011] ; Chinese Academy of Sciences, China ( to K. D.), and National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09103-071]
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000293078200040
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
源URL[http://119.78.100.183/handle/2S10ELR8/278469]  
专题药理学第三研究室
通讯作者Jiang, Songshan
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Glycochem & Glycobiol Lab, Shanghai 200031, Peoples R China;
2.NW A&F Univ, Coll Sci, Yangling, Shanxi, Peoples R China;
3.Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Guangzhou 510275, Guangdong, Peoples R China;
4.Sun Yat Sen Univ, Sch Life Sci, MOE Key Lab Gene Engn, Guangzhou 510275, Guangdong, Peoples R China
推荐引用方式
GB/T 7714		 Shen, Xiaokun,Fang, Jianping,Lv, Xiaofen,et al. Heparin Impairs Angiogenesis through Inhibition of MicroRNA-10b[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(30):26616-26627.
APA Shen, Xiaokun.,Fang, Jianping.,Lv, Xiaofen.,Pei, Zhicao.,Wang, Ying.,...&Ding, Kan.(2011).Heparin Impairs Angiogenesis through Inhibition of MicroRNA-10b.JOURNAL OF BIOLOGICAL CHEMISTRY,286(30),26616-26627.
MLA Shen, Xiaokun,et al."Heparin Impairs Angiogenesis through Inhibition of MicroRNA-10b".JOURNAL OF BIOLOGICAL CHEMISTRY 286.30(2011):26616-26627.

入库方式： OAI收割

来源：上海药物研究所

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