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

Journal of Extracellular Vesicles
Emanuela MensàFabiola Olivieri

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...Continue Reading

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Citations

Oct 8, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Antero Salminen
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Datasets Mentioned

BETA
EV190105
PRJEB33703

Methods Mentioned

BETA
PCR
RNAseq
size-exclusion
transmission electron microscopy
transfection
flow cytometry
PCA
ChIP-Seq
Assay

Software Mentioned

ShinyMethyl
EpiTYPER
Minfi
NanoSight NTA
TargetScan
GeneSpring GX
DIANA
DESeq2 bioconductor
miRNome
Ingenuity Pathway Analysis ( IPA )

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