Abstract
| Original language | English |
|---|---|
| Journal | Sci. Rep. |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2020 |
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Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs : Scientific Reports. / Giuliani, A.; Londin, E.; Ferracin, M.; Mensà, E.; Prattichizzo, F.; Ramini, D.; Marcheselli, F.; Recchioni, R.; Rippo, M.R.; Bonafè, M.; Rigoutsos, I.; Olivieri, F.; Sabbatinelli, J.
In: Sci. Rep., Vol. 10, No. 1, 2020.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs
T2 - Scientific Reports
AU - Giuliani, A.
AU - Londin, E.
AU - Ferracin, M.
AU - Mensà, E.
AU - Prattichizzo, F.
AU - Ramini, D.
AU - Marcheselli, F.
AU - Recchioni, R.
AU - Rippo, M.R.
AU - Bonafè, M.
AU - Rigoutsos, I.
AU - Olivieri, F.
AU - Sabbatinelli, J.
N1 - Export Date: 5 March 2021 Correspondence Address: Olivieri, F.; Department of Clinical and Molecular Sciences, Via Tronto 10/A, Italy; email: f.olivieri@univpm.it Funding details: Ministero della Salute, Ricerca corrente Funding details: Università Politecnica delle Marche, UNIVPM, RSA grant Funding text 1: This work was supported by grants from Università Politecnica delle Marche [Scientific research grant, years 2017–2018–2019 to F.O. and M.R.R.] and by the Italian Ministry of Health [“Ricerca corrente” to IRCCS INRCA and IRCCS MultiMedica]. References: Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020 (2020) Diabetes Care, 43, pp. SS98-S110. , https://doi.org/10.2337/dc20-S009, 1, . 9, , . doi:, (,); Salvatore, T., Metformin: an old drug against old age and associated morbidities (2020) Diabetes Res. Clin. 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PY - 2020
Y1 - 2020
N2 - 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. © 2020, The Author(s).
AB - 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. © 2020, The Author(s).
U2 - 10.1038/s41598-020-78871-5
DO - 10.1038/s41598-020-78871-5
M3 - Article
VL - 10
JO - Sci. Rep.
JF - Sci. Rep.
SN - 2045-2322
IS - 1
ER -