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 |
Appears in Collections: | Articles |
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