TY  - JOUR
A1  - Voellenkle, Christine
A1  - Garcia-Manteiga, Jose Manuel
A1  - Pedrott, Simona
A1  - De Toma, Ilario
A1  - Da Silva, Daniel
A1  - Maimone, Biagina
A1  - Greco, Simona
A1  - Fasanaro, Pasquale
A1  - Creo, Pasquale
A1  - Zaccagnini, Germana
A1  - Gaetano, Carlo
A1  - Martelli, Fabio
T1  - Implication of long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing
T2  - Scientific reports
N2  - Long noncoding RNAs (lncRNAs) are non-protein coding RNAs regulating gene expression. Although for some lncRNAs a relevant role in hypoxic endothelium has been shown, the regulation and function of lncRNAs is still largely unknown in the vascular physio-pathology. Taking advantage of next-generation sequencing techniques, transcriptomic changes induced by endothelial cell exposure to hypoxia were investigated. Paired-end sequencing of polyadenylated RNA derived from human umbilical vein endothelial cells (HUVECs) exposed to 1% O2 or normoxia was performed. Bioinformatics analysis identified ≈2000 differentially expressed genes, including 122 lncRNAs. Extensive validation was performed by both microarray and qPCR. Among the validated lncRNAs, H19, MIR210HG, MEG9, MALAT1 and MIR22HG were also induced in a mouse model of hindlimb ischemia. To test the functional relevance of lncRNAs in endothelial cells, knockdown of H19 expression was performed. H19 inhibition decreased HUVEC growth, inducing their accumulation in G1 phase of the cell cycle; accordingly, p21 (CDKN1A) expression was increased. Additionally, H19 knockdown also diminished HUVEC ability to form capillary like structures when plated on matrigel. In conclusion, a high-confidence signature of lncRNAs modulated by hypoxia in HUVEC was identified and a significant impact of H19 lncRNA was shown.
KW  - Cardiology
KW  - Molecular biology
KW  - Non-coding RNAs
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43014
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-430143
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827084
SN  - 2045-2322
N1  - This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
VL  - 6
IS  - Article number: 24141
SP  - 1
EP  - 13
PB  - Nature Publishing Group
CY  - London
ER  -