Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract

Abstract Background Electronic-cigarette (e-cig) usage, particularly in the youth population, is a growing concern. It is known that e-cig causes endothelial dysfunction, which is a risk factor for the development of cardiovascular diseases; however, the mechanisms involved remain unclear. We hypoth...

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Autores principales:	Hoai Huong Thi Le, Chen-wei Liu, Philip Denaro, Jordan Jousma, Ning-Yi Shao, Irfan Rahman, Won Hee Lee
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	lncRNAs e-cigarettes iPSC-ECs fatty acid oxidation endothelial dysfunction Medicine (General) R5-920 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/4d9bf44c47ce4c68bd0f6f829f68a101
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spelling	oai:doaj.org-article:4d9bf44c47ce4c68bd0f6f829f68a1012021-12-05T12:05:42ZGenome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract10.1186/s13287-021-02654-61757-6512https://doaj.org/article/4d9bf44c47ce4c68bd0f6f829f68a1012021-12-01T00:00:00Zhttps://doi.org/10.1186/s13287-021-02654-6https://doaj.org/toc/1757-6512Abstract Background Electronic-cigarette (e-cig) usage, particularly in the youth population, is a growing concern. It is known that e-cig causes endothelial dysfunction, which is a risk factor for the development of cardiovascular diseases; however, the mechanisms involved remain unclear. We hypothesized that long noncoding RNAs (lncRNAs) may play a role in e-cig-induced endothelial dysfunction. Methods Here, we identified lncRNAs that are dysregulated in human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) following 24 h of e-cig aerosol extract treatment via microarray analysis. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analyses of the dysregulated mRNAs following e-cig exposure and constructed co-expression networks of the top 5 upregulated lncRNAs and the top 5 downregulated lncRNAs and the mRNAs that are correlated with them. Furthermore, the functional effects of knocking down lncRNA lung cancer-associated transcript 1 (LUCAT1) on EC phenotypes were determined as it was one of the significantly upregulated lncRNAs following e-cig exposure based on our profiling. Results 183 lncRNAs and 132 mRNAs were found to be upregulated, whereas 297 lncRNAs and 413 mRNAs were found to be downregulated after e-cig exposure. We also observed that e-cig caused dysregulation of endothelial metabolism resulting in increased FAO activity, higher mitochondrial membrane potential, and decreased glucose uptake and glycolysis. These results suggest that e-cig alters EC metabolism by increasing FAO to compensate for energy deficiency in ECs. Finally, the knockdown of LUCAT1 prevented e-cig-induced EC dysfunction by maintaining vascular barrier, reducing reactive oxygen species level, and increasing migration capacity. Conclusion This study identifies an expression profile of differentially expressed lncRNAs and several potential regulators and pathways in ECs exposed to e-cig, which provide insights into the regulation of lncRNAs and mRNAs and the role of lncRNA and mRNA networks in ECs associated e-cig exposure.Hoai Huong Thi LeChen-wei LiuPhilip DenaroJordan JousmaNing-Yi ShaoIrfan RahmanWon Hee LeeBMCarticlelncRNAse-cigarettesiPSC-ECsfatty acid oxidationendothelial dysfunctionMedicine (General)R5-920BiochemistryQD415-436ENStem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lncRNAs e-cigarettes iPSC-ECs fatty acid oxidation endothelial dysfunction Medicine (General) R5-920 Biochemistry QD415-436
spellingShingle	lncRNAs e-cigarettes iPSC-ECs fatty acid oxidation endothelial dysfunction Medicine (General) R5-920 Biochemistry QD415-436 Hoai Huong Thi Le Chen-wei Liu Philip Denaro Jordan Jousma Ning-Yi Shao Irfan Rahman Won Hee Lee Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract
description	Abstract Background Electronic-cigarette (e-cig) usage, particularly in the youth population, is a growing concern. It is known that e-cig causes endothelial dysfunction, which is a risk factor for the development of cardiovascular diseases; however, the mechanisms involved remain unclear. We hypothesized that long noncoding RNAs (lncRNAs) may play a role in e-cig-induced endothelial dysfunction. Methods Here, we identified lncRNAs that are dysregulated in human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) following 24 h of e-cig aerosol extract treatment via microarray analysis. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analyses of the dysregulated mRNAs following e-cig exposure and constructed co-expression networks of the top 5 upregulated lncRNAs and the top 5 downregulated lncRNAs and the mRNAs that are correlated with them. Furthermore, the functional effects of knocking down lncRNA lung cancer-associated transcript 1 (LUCAT1) on EC phenotypes were determined as it was one of the significantly upregulated lncRNAs following e-cig exposure based on our profiling. Results 183 lncRNAs and 132 mRNAs were found to be upregulated, whereas 297 lncRNAs and 413 mRNAs were found to be downregulated after e-cig exposure. We also observed that e-cig caused dysregulation of endothelial metabolism resulting in increased FAO activity, higher mitochondrial membrane potential, and decreased glucose uptake and glycolysis. These results suggest that e-cig alters EC metabolism by increasing FAO to compensate for energy deficiency in ECs. Finally, the knockdown of LUCAT1 prevented e-cig-induced EC dysfunction by maintaining vascular barrier, reducing reactive oxygen species level, and increasing migration capacity. Conclusion This study identifies an expression profile of differentially expressed lncRNAs and several potential regulators and pathways in ECs exposed to e-cig, which provide insights into the regulation of lncRNAs and mRNAs and the role of lncRNA and mRNA networks in ECs associated e-cig exposure.
format	article
author	Hoai Huong Thi Le Chen-wei Liu Philip Denaro Jordan Jousma Ning-Yi Shao Irfan Rahman Won Hee Lee
author_facet	Hoai Huong Thi Le Chen-wei Liu Philip Denaro Jordan Jousma Ning-Yi Shao Irfan Rahman Won Hee Lee
author_sort	Hoai Huong Thi Le
title	Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract
title_short	Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract
title_full	Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract
title_fullStr	Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract
title_full_unstemmed	Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract
title_sort	genome-wide differential expression profiling of lncrnas and mrnas in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract
publisher	BMC
publishDate	2021
url	https://doaj.org/article/4d9bf44c47ce4c68bd0f6f829f68a101
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Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract

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