MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Global microRNA depletion suppresses tumor angiogenesis

Author(s)
Chen, Sidi; Xue, Yuan; Le, Cong; Bhutkar, Arjun (AJ); Bell, Eric L.; Zhang, Feng; Langer, Robert; Sharp, Phillip A.; Wu, Xuebing, Ph. D. Massachusetts Institute of Technology; Wu, Xuebing, Ph. D. Massachusetts Institute of Technology; ... Show more Show less
Thumbnail
DownloadChen-2014-Global microRNA depl.pdf (2.610Mb)
PUBLISHER_CC

Publisher with Creative Commons License

Creative Commons Attribution

Terms of use
Creative Commons Attribution-Noncommerical http://creativecommons.org/licenses/by-nc/4.0
Metadata
Show full item record
Abstract
MicroRNAs delicately regulate the balance of angiogenesis. Here we show that depletion of all microRNAs suppresses tumor angiogenesis. We generated microRNA-deficient tumors by knocking out Dicer1. These tumors are highly hypoxic but poorly vascularized, suggestive of deficient angiogenesis signaling. Expression profiling revealed that angiogenesis genes were significantly down-regulated as a result of the microRNA deficiency. Factor inhibiting hypoxia-inducible factor 1 (HIF-1), FIH1, is derepressed under these conditions and suppresses HIF transcription. Knocking out FIH1 using CRISPR/Cas9-mediated genome engineering reversed the phenotypes of microRNA-deficient cells in HIF transcriptional activity, VEGF production, tumor hypoxia, and tumor angiogenesis. Using multiplexed CRISPR/Cas9, we deleted regions in FIH1 3′ untranslated regions (UTRs) that contain microRNA-binding sites, which derepresses FIH1 protein and represses hypoxia response. These data suggest that microRNAs promote tumor responses to hypoxia and angiogenesis by repressing FIH1.
Date issued
2014-05
URI
http://hdl.handle.net/1721.1/91982
Department
Massachusetts Institute of Technology. Computational and Systems Biology Program; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemical Engineering; Koch Institute for Integrative Cancer Research at MIT
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory Press
Citation
Chen, S., Y. Xue, X. Wu, C. Le, A. Bhutkar, E. L. Bell, F. Zhang, R. Langer, and P. A. Sharp. “Global microRNA Depletion Suppresses Tumor Angiogenesis.” Genes & Development 28, no. 10 (May 15, 2014): 1054–1067.
Version: Final published version
ISSN
0890-9369

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.