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MicroRNA as crucial regulators of gene expression in estradiol-treated human endothelial cells.

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MicroRNA as crucial regulators of gene expression in estradiol-treated human endothelial cells.

dc.contributor.author	Vidal-Gómez, Xavier
dc.contributor.author	Pérez-Cremades, Daniel
dc.contributor.author	Mompeón, Ana
dc.contributor.author	Dantas, A. P.
dc.contributor.author	Novella, Susana
dc.contributor.author	Hermenegildo, Carlos
dc.date.accessioned	2020-09-30T15:21:47Z
dc.date.available	2020-09-30T15:21:47Z
dc.date.issued	2018
dc.identifier.citation	Vidal-Gómez, Xavier Pérez-Cremades, Daniel Mompeón, Ana Dantas, A. P. Novella, Susana Hermenegildo, Carlos 2018 MicroRNA as crucial regulators of gene expression in estradiol-treated human endothelial cells. Cellular Physiology and Biochemistry 45 1878 1892
dc.identifier.uri	https://hdl.handle.net/10550/75704
dc.description.abstract	Background/Aims: Estrogen signalling plays an important role in vascular biology as it modulates vasoactive and metabolic pathways in endothelial cells. Growing evidence has also established microRNA (miRNA) as key regulators of endothelial function. Nonetheless, the role of estrogen regulation on miRNA profile in endothelial cells is poorly understood. In this study, we aimed to determine how estrogen modulates miRNA profile in human endothelial cells and to explore the role of the different estrogen receptors (ERα, ERβ and GPER) in the regulation of miRNA expression by estrogen. Methods: We used miRNA microarrays to determine global miRNA expression in human umbilical vein endothelial cells (HUVEC) exposed to a physiological concentration of estradiol (E2; 1 nmol/L) for 24 hours. miRNA-gene interactions were computationally predicted using Ingenuity Pathway Analysis and changes in miRNA levels were validated by qRT-PCR. Role of ER in the E2-induced miRNA was additionally confirmed by using specific ER agonists and antagonists. Results: miRNA array revealed that expression of 114 miRNA were significantly modified after E2 exposition. Further biological pathway analysis revealed cell death and survival, lipid metabolism, reproductive system function, as the top functions regulated by E2. We validated changes in the most significantly increased (miR-30b-5p, miR-487a-5p, miR-4710, miR-501-3p) and decreased (miR-378h and miR-1244) miRNA and the role of ER in these E2-induced miRNA was determined. Results showed that both classical, ERα and ERβ, and membrane-bound ER, GPER, differentially regulated specific miRNA. In silico analysis of validated miRNA promoters identified specific ER binding sites. Conclusion: Our findings identify differentially expressed miRNA pathways linked to E2 in human endothelial cells through ER, and provide new insights by which estrogen can modulate endothelial function.
dc.language.iso	eng
dc.relation.ispartof	Cellular Physiology and Biochemistry, 2018, vol. 45, p. 1878-1892
dc.subject	Cèl·lules
dc.subject	Receptors d'hormones
dc.title	MicroRNA as crucial regulators of gene expression in estradiol-treated human endothelial cells.
dc.type	journal article	es_ES
dc.date.updated	2020-09-30T15:21:47Z
dc.identifier.doi	10.1159/000487910
dc.identifier.idgrec	130187
dc.rights.accessRights	open access	es_ES