Deep-sequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs

Voellenkle, Christine, van Rooij, Jeroen, Guffanti, Alessandro, Brini, Elena, Fasanaro, Pasquale, Isaia, Eleonora, Croft, Larry, David, Matei, Capogrossi, Maurizio C., Moles, Anna, Felsani, Armando and Martelli, Fabio (2012) Deep-sequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs. RNA, 18 3: 472-484. doi:10.1261/rna.027615.111

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Author Voellenkle, Christine
van Rooij, Jeroen
Guffanti, Alessandro
Brini, Elena
Fasanaro, Pasquale
Isaia, Eleonora
Croft, Larry
David, Matei
Capogrossi, Maurizio C.
Moles, Anna
Felsani, Armando
Martelli, Fabio
Title Deep-sequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs
Journal name RNA   Check publisher's open access policy
ISSN 1355-8382
1469-9001
Publication date 2012-03
Sub-type Article (original research)
DOI 10.1261/rna.027615.111
Open Access Status File (Publisher version)
Volume 18
Issue 3
Start page 472
End page 484
Total pages 13
Place of publication Woodbury, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Collection year 2013
Language eng
Formatted abstract
In order to understand the role of microRNAs (miRNAs) in vascular physiopathology, we took advantage of deep-sequencing techniques to accurately and comprehensively profile the entire miRNA population expressed by endothelial cells exposed to hypoxia. SOLiD sequencing of small RNAs derived from human umbilical vein endothelial cells (HUVECs) exposed to 1% O2 or normoxia for 24 h yielded more than 22 million reads per library. A customized bioinformatic pipeline identified more than 400 annotated microRNA/microRNA* species with a broad abundance range: miR-21 and miR-126 totaled almost 40% of all miRNAs. A complex repertoire of isomiRs was found, displaying also 5' variations, potentially affecting target recognition. Highstringency bioinformatic analysis identified microRNA candidates, whose predicted pre-miRNAs folded into a stable hairpin. Validation of a subset by qPCR identified 18 high-confidence novel miRNAs as detectable in independent HUVEC cultures and associated to the RISC complex. The expression of two novel miRNAs was significantly down-modulated by hypoxia, while miR-210 was significantly induced. Gene ontology analysis of their predicted targets revealed a significant association to hypoxiainducible factor signaling, cardiovascular diseases, and cancer. Overexpression of the novel miRNAs in hypoxic endothelial cells affected cell growth and confirmed the biological relevance of their down-modulation. In conclusion, deep-sequencing accurately profiled known, variant, and novel microRNAs expressed by endothelial cells in normoxia and hypoxia.
Keyword microRNA
isomiR
deep-sequencing
hypoxia
endothelium
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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