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ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells
OBJECTIVE: Regulation of intercellular adhesion molecule (ICAM)-1 in retinal endothelial cells is a promising druggable target for retinal vascular diseases. The ICAM-1-related (ICR) long non-coding RNA stabilizes ICAM-1 transcript, increasing protein expression. However, studies of ICR involvement...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944171/ https://www.ncbi.nlm.nih.gov/pubmed/29743093 http://dx.doi.org/10.1186/s13104-018-3384-8 |
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author | Lumsden, Amanda L. Ma, Yuefang Ashander, Liam M. Stempel, Andrew J. Keating, Damien J. Smith, Justine R. Appukuttan, Binoy |
author_facet | Lumsden, Amanda L. Ma, Yuefang Ashander, Liam M. Stempel, Andrew J. Keating, Damien J. Smith, Justine R. Appukuttan, Binoy |
author_sort | Lumsden, Amanda L. |
collection | PubMed |
description | OBJECTIVE: Regulation of intercellular adhesion molecule (ICAM)-1 in retinal endothelial cells is a promising druggable target for retinal vascular diseases. The ICAM-1-related (ICR) long non-coding RNA stabilizes ICAM-1 transcript, increasing protein expression. However, studies of ICR involvement in disease have been limited as the promoter is uncharacterized. To address this issue, we undertook a comprehensive in silico analysis of the human ICR gene promoter region. RESULTS: We used genomic evolutionary rate profiling to identify a 115 base pair (bp) sequence within 500 bp upstream of the transcription start site of the annotated human ICR gene that was conserved across 25 eutherian genomes. A second constrained sequence upstream of the orthologous mouse gene (68 bp; conserved across 27 Eutherian genomes including human) was also discovered. Searching these elements identified 33 matrices predictive of binding sites for transcription factors known to be responsive to a broad range of pathological stimuli, including hypoxia, and metabolic and inflammatory proteins. Five phenotype-associated single nucleotide polymorphisms (SNPs) in the immediate vicinity of these elements included four SNPs (i.e. rs2569693, rs281439, rs281440 and rs11575074) predicted to impact binding motifs of transcription factors, and thus the expression of ICR and ICAM-1 genes, with potential to influence disease susceptibility. We verified that human retinal endothelial cells expressed ICR, and observed induction of expression by tumor necrosis factor-α. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3384-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5944171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59441712018-05-14 ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells Lumsden, Amanda L. Ma, Yuefang Ashander, Liam M. Stempel, Andrew J. Keating, Damien J. Smith, Justine R. Appukuttan, Binoy BMC Res Notes Research Note OBJECTIVE: Regulation of intercellular adhesion molecule (ICAM)-1 in retinal endothelial cells is a promising druggable target for retinal vascular diseases. The ICAM-1-related (ICR) long non-coding RNA stabilizes ICAM-1 transcript, increasing protein expression. However, studies of ICR involvement in disease have been limited as the promoter is uncharacterized. To address this issue, we undertook a comprehensive in silico analysis of the human ICR gene promoter region. RESULTS: We used genomic evolutionary rate profiling to identify a 115 base pair (bp) sequence within 500 bp upstream of the transcription start site of the annotated human ICR gene that was conserved across 25 eutherian genomes. A second constrained sequence upstream of the orthologous mouse gene (68 bp; conserved across 27 Eutherian genomes including human) was also discovered. Searching these elements identified 33 matrices predictive of binding sites for transcription factors known to be responsive to a broad range of pathological stimuli, including hypoxia, and metabolic and inflammatory proteins. Five phenotype-associated single nucleotide polymorphisms (SNPs) in the immediate vicinity of these elements included four SNPs (i.e. rs2569693, rs281439, rs281440 and rs11575074) predicted to impact binding motifs of transcription factors, and thus the expression of ICR and ICAM-1 genes, with potential to influence disease susceptibility. We verified that human retinal endothelial cells expressed ICR, and observed induction of expression by tumor necrosis factor-α. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3384-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-09 /pmc/articles/PMC5944171/ /pubmed/29743093 http://dx.doi.org/10.1186/s13104-018-3384-8 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Note Lumsden, Amanda L. Ma, Yuefang Ashander, Liam M. Stempel, Andrew J. Keating, Damien J. Smith, Justine R. Appukuttan, Binoy ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells |
title | ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells |
title_full | ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells |
title_fullStr | ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells |
title_full_unstemmed | ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells |
title_short | ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells |
title_sort | icam-1-related long non-coding rna: promoter analysis and expression in human retinal endothelial cells |
topic | Research Note |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944171/ https://www.ncbi.nlm.nih.gov/pubmed/29743093 http://dx.doi.org/10.1186/s13104-018-3384-8 |
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