標題: Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis
作者: Chen, Zhen
Lai, Tsung-Ching
Jan, Yi-Hua
Lin, Feng-Mao
Wang, Wei-Chi
Xiao, Han
Wang, Yun-Ting
Sun, Wei
Cui, Xiaopei
Li, Ying-Shiuan
Fang, Tzan
Zhao, Hongwei
Padmanabhan, Chellappan
Sun, Ruobai
Wang, Danny Ling
Jin, Hailing
Chau, Gar-Yang
Huang, Hsien-Da
Hsiao, Michael
Shyy, John Y-J.
生物資訊及系統生物研究所
Institude of Bioinformatics and Systems Biology
公開日期: 1-Mar-2013
摘要: Despite a general repression of translation under hypoxia, cells selectively upregulate a set of hypoxia-inducible genes. Results from deep sequencing revealed that Let-7 and miR-103/107 are hypoxia-responsive microRNAs (HRMs) that are strongly induced in vascular endothelial cells. In silico bioinformatics and in vitro validation showed that these HRMs are induced by HIF1 alpha and target argonaute 1 (AGO1), which anchors the microRNA-induced silencing complex (miRISC). HRM targeting of AGO1 resulted in the translational desuppression of VEGF mRNA. Inhibition of HRM or overexpression of AGO1 without the 3' untranslated region decreased hypoxia-induced angiogenesis. Conversely, AGO1 knockdown increased angiogenesis under normoxia in vivo. In addition, data from tumor xenografts and human cancer specimens indicate that AGO1-mediated translational desuppression of VEGF may be associated with tumor angiogenesis and poor prognosis. These fmdings provide evidence for an angiogenic pathway involving HRMs that target AGO1 and suggest that this pathway may be a suitable target for anti- or proangiogenesis strategies.
URI: http://dx.doi.org/10.1172/JCI65344
http://hdl.handle.net/11536/21419
ISSN: 0021-9738
DOI: 10.1172/JCI65344
期刊: JOURNAL OF CLINICAL INVESTIGATION
Volume: 123
Issue: 3
起始頁: 1057
結束頁: 1067
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