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Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells.


ABSTRACT: The role of epigenetics in endothelial cell senescence is a cutting-edge topic in ageing research. However, little is known of the relative contribution to pro-senescence signal propagation provided by microRNAs shuttled by extracellular vesicles (EVs) released from senescent cells. Analysis of microRNA and DNA methylation profiles in non-senescent (control) and senescent (SEN) human umbilical vein endothelial cells (HUVECs), and microRNA profiling of their cognate small EVs (sEVs) and large EVs demonstrated that SEN cells released a significantly greater sEV number than control cells. sEVs were enriched in miR-21-5p and miR-217, which target DNMT1 and SIRT1. Treatment of control cells with SEN sEVs induced a miR-21/miR-217-related impairment of DNMT1-SIRT1 expression, the reduction of proliferation markers, the acquisition of a senescent phenotype and a partial demethylation of the locus encoding for miR-21. MicroRNA profiling of sEVs from plasma of healthy subjects aged 40-100 years showed an inverse U-shaped age-related trend for miR-21-5p, consistent with senescence-associated biomarker profiles. Our findings suggest that miR-21-5p/miR-217 carried by SEN sEVs spread pro-senescence signals, affecting DNA methylation and cell replication.

SUBMITTER: Mensa E 

PROVIDER: S-EPMC7048230 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells.

Mensà Emanuela E   Guescini Michele M   Giuliani Angelica A   Bacalini Maria Giulia MG   Ramini Deborah D   Corleone Giacomo G   Ferracin Manuela M   Fulgenzi Gianluca G   Graciotti Laura L   Prattichizzo Francesco F   Sorci Leonardo L   Battistelli Michela M   Monsurrò Vladia V   Bonfigli Anna Rita AR   Cardelli Maurizio M   Recchioni Rina R   Marcheselli Fiorella F   Latini Silvia S   Maggio Serena S   Fanelli Mirco M   Amatori Stefano S   Storci Gianluca G   Ceriello Antonio A   Stocchi Vilberto V   De Luca Maria M   Magnani Luca L   Rippo Maria Rita MR   Procopio Antonio Domenico AD   Procopio Antonio Domenico AD   Sala Claudia C   Budimir Iva I   Bassi Cristian C   Negrini Massimo M   Garagnani Paolo P   Franceschi Claudio C   Sabbatinelli Jacopo J   Bonafè Massimiliano M   Olivieri Fabiola F  

Journal of extracellular vesicles 20200218 1


The role of epigenetics in endothelial cell senescence is a cutting-edge topic in ageing research. However, little is known of the relative contribution to pro-senescence signal propagation provided by microRNAs shuttled by extracellular vesicles (EVs) released from senescent cells. Analysis of microRNA and DNA methylation profiles in non-senescent (control) and senescent (SEN) human umbilical vein endothelial cells (HUVECs), and microRNA profiling of their cognate small EVs (sEVs) and large EVs  ...[more]

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