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Implication of Long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing.

ABSTRACT: 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.

SUBMITTER: Voellenkle C

PROVIDER: S-EPMC4827084 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Implication of Long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing.

Voellenkle C C Garcia-Manteiga J M JM Pedrotti S S Perfetti A A De Toma I I Da Silva D D Maimone B B Greco S S Fasanaro P P Creo P P Zaccagnini G G Gaetano C C Martelli F F

Scientific reports 20160411

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 endothel ...[more]

PMID: 27063004

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Project description:PurposeExosomes are able to exchange their bioactive RNA cargo to recipient cells. In COPD, exosomes can be controlled and engineered for its use as targeted diagnostic and therapeutic tool. Our study explored novel lncRNAs and mRNAs in plasma exosomes that could be involved in the pathogenesis of COPD.MethodsHigh-throughput sequencing was conducted to detect the alterations in the expression of exosomal lncRNAs and mRNAs. Gene ontology (GO) functional analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to determine the significant functions and pathways associated with differentially expressed (DE) lncRNAs. The mRNA expression profile dataset, GSE76925, and microRNA expression profile dataset, GSE70080, were obtained from the GEO database. Venn diagrams were used to find common DE mRNAs between my mRNAs dataset and GSE76925. These common DEGs were subjected to PPI analyses to identify Hub genes. Subsequently, Venn diagrams were used to identify common genes between the target genes of DE-miRNAs and Hub genes as well as DE-miRNAs and my lncRNAs dataset. Finally, a lncRNA-miRNA-mRNA co-expression network was constructed by prediction using proprietary software. The lncRNA and mRNA expressions were then validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR).ResultsWe identified 1578 differentially regulated lncRNAs and 3071 differentially regulated mRNAs. GO and KEGG pathway analyses suggested that the DE lncRNAs are involved in the pathogenesis of COPD. A lncRNA-miRNA-mRNA meshwork was established to predict the potential interactions among these RNAs. RP3-329A5.8 and MRPS11 expression was then subjected to qRT-PCR for validation. Correlations between MRPS11 and clinic-pathological features were explored.ConclusionOur study provided a set of lncRNAs and mRNAs that may be involved in the pathogenesis of COPD, thereby highlighting the need for further research on both diagnostic biomarkers and molecular mechanisms.

Dataset Information

Implication of Long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing.

Publications

Implication of Long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing.

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