Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs

Abstract Increasing evidence suggest that the glucose-lowering drug metformin exerts a valuable anti-senescence role. The ability of metformin to affect the biogenesis of selected microRNAs (miRNAs) was recently suggested. MicroRNA isoforms (isomiRs) are distinct variations of miRNA sequences, harbo...

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Autores principales:	Angelica Giuliani, Eric Londin, Manuela Ferracin, Emanuela Mensà, Francesco Prattichizzo, Deborah Ramini, Fiorella Marcheselli, Rina Recchioni, Maria Rita Rippo, Massimiliano Bonafè, Isidore Rigoutsos, Fabiola Olivieri, Jacopo Sabbatinelli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9db56585c5b24fc0af64d8a7a31bcb9d
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spelling	oai:doaj.org-article:9db56585c5b24fc0af64d8a7a31bcb9d2021-12-02T15:11:51ZLong-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs10.1038/s41598-020-78871-52045-2322https://doaj.org/article/9db56585c5b24fc0af64d8a7a31bcb9d2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78871-5https://doaj.org/toc/2045-2322Abstract Increasing evidence suggest that the glucose-lowering drug metformin exerts a valuable anti-senescence role. The ability of metformin to affect the biogenesis of selected microRNAs (miRNAs) was recently suggested. MicroRNA isoforms (isomiRs) are distinct variations of miRNA sequences, harboring addition or deletion of one or more nucleotides at the 5′ and/or 3′ ends of the canonical miRNA sequence. We performed a comprehensive analysis of miRNA and isomiR profile in human endothelial cells undergoing replicative senescence in presence of metformin. Metformin treatment was associated with the differential expression of 27 miRNAs (including miR-100-5p, -125b-5p, -654-3p, -217 and -216a-3p/5p). IsomiR analysis revealed that almost 40% of the total miRNA pool was composed by non-canonical sequences. Metformin significantly affects the relative abundance of 133 isomiRs, including the non-canonical forms of the aforementioned miRNAs. Pathway enrichment analysis suggested that pathways associated with proliferation and nutrient sensing are modulated by metformin-regulated miRNAs and that some of the regulated isomiRs (e.g. the 5′ miR-217 isomiR) are endowed with alternative seed sequences and share less than half of the predicted targets with the canonical form. Our results show that metformin reshapes the senescence-associated miRNA/isomiR patterns of endothelial cells, thus expanding our insight into the cell senescence molecular machinery.Angelica GiulianiEric LondinManuela FerracinEmanuela MensàFrancesco PrattichizzoDeborah RaminiFiorella MarcheselliRina RecchioniMaria Rita RippoMassimiliano BonafèIsidore RigoutsosFabiola OlivieriJacopo SabbatinelliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angelica Giuliani Eric Londin Manuela Ferracin Emanuela Mensà Francesco Prattichizzo Deborah Ramini Fiorella Marcheselli Rina Recchioni Maria Rita Rippo Massimiliano Bonafè Isidore Rigoutsos Fabiola Olivieri Jacopo Sabbatinelli Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs
description	Abstract Increasing evidence suggest that the glucose-lowering drug metformin exerts a valuable anti-senescence role. The ability of metformin to affect the biogenesis of selected microRNAs (miRNAs) was recently suggested. MicroRNA isoforms (isomiRs) are distinct variations of miRNA sequences, harboring addition or deletion of one or more nucleotides at the 5′ and/or 3′ ends of the canonical miRNA sequence. We performed a comprehensive analysis of miRNA and isomiR profile in human endothelial cells undergoing replicative senescence in presence of metformin. Metformin treatment was associated with the differential expression of 27 miRNAs (including miR-100-5p, -125b-5p, -654-3p, -217 and -216a-3p/5p). IsomiR analysis revealed that almost 40% of the total miRNA pool was composed by non-canonical sequences. Metformin significantly affects the relative abundance of 133 isomiRs, including the non-canonical forms of the aforementioned miRNAs. Pathway enrichment analysis suggested that pathways associated with proliferation and nutrient sensing are modulated by metformin-regulated miRNAs and that some of the regulated isomiRs (e.g. the 5′ miR-217 isomiR) are endowed with alternative seed sequences and share less than half of the predicted targets with the canonical form. Our results show that metformin reshapes the senescence-associated miRNA/isomiR patterns of endothelial cells, thus expanding our insight into the cell senescence molecular machinery.
format	article
author	Angelica Giuliani Eric Londin Manuela Ferracin Emanuela Mensà Francesco Prattichizzo Deborah Ramini Fiorella Marcheselli Rina Recchioni Maria Rita Rippo Massimiliano Bonafè Isidore Rigoutsos Fabiola Olivieri Jacopo Sabbatinelli
author_facet	Angelica Giuliani Eric Londin Manuela Ferracin Emanuela Mensà Francesco Prattichizzo Deborah Ramini Fiorella Marcheselli Rina Recchioni Maria Rita Rippo Massimiliano Bonafè Isidore Rigoutsos Fabiola Olivieri Jacopo Sabbatinelli
author_sort	Angelica Giuliani
title	Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs
title_short	Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs
title_full	Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs
title_fullStr	Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs
title_full_unstemmed	Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs
title_sort	long-term exposure of human endothelial cells to metformin modulates mirnas and isomirs
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/9db56585c5b24fc0af64d8a7a31bcb9d
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Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs

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