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Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets.

ABSTRACT: Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched with cargo involved in multiple cancers (glycolytic enzymes, TGFBI, miR-1246, MET, GPC1 and AGO2), Alzheimer's disease (APP) and cardiovascular disease (ACE2, ACE and PCSK9). The majority of extracellular RNA is associated with supermeres rather than small extracellular vesicles and exomeres. Cancer-derived supermeres increase lactate secretion, transfer cetuximab resistance and decrease hepatic lipids and glycogen in vivo. This study identifies a distinct functional nanoparticle replete with potential circulating biomarkers and therapeutic targets for a host of human diseases.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC8656144 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets.

Zhang Qin Q Jeppesen Dennis K DK Higginbotham James N JN Graves-Deal Ramona R Trinh Vincent Q VQ Ramirez Marisol A MA Sohn Yoojin Y Neininger Abigail C AC Taneja Nilay N McKinley Eliot T ET Niitsu Hiroaki H Cao Zheng Z Evans Rachel R Glass Sarah E SE Ray Kevin C KC Fissell William H WH Hill Salisha S Rose Kristie Lindsey KL Huh Won Jae WJ Washington Mary Kay MK Ayers Gregory Daniel GD Burnette Dylan T DT Sharma Shivani S Rome Leonard H LH Franklin Jeffrey L JL Lee Youngmin A YA Liu Qi Q Coffey Robert J RJ

Nature cell biology 20211209 12

Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched ...[more]

PMID: 34887515

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Project description:BackgroundCoronary artery disease (CAD) is a complex illness with unknown pathophysiology. Peripheral biomarkers are a non-invasive method required to track the onset and progression of CAD and have unbeatable benefits in terms of early identification, prognostic assessment, and categorization of the diagnosis. This study aimed to identify and validate the diagnostic and therapeutic potential of differentially expressed immune-related genes (DE-IRGs) in CAD, which will aid in improving our knowledge on the etiology of CAD and in forming genetic predictions.MethodsFirst, we searched coronary heart disease in the Gene Expression Omnibus (GEO) database and identified GSE20680 (CAD = 87, Normal = 52) as the trial set and GSE20681 (CAD = 99, Normal = 99) as the validation set. Functional enrichment analysis using protein-protein interactions (PPIs), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out on the identified differentially expressed genes. Optimal feature genes (OFGs) were generated using the support vector machine recursive feature elimination algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm. Furthermore, immune infiltration in CAD patients and healthy controls was compared using CIBERSORT, and the relationship between immune cells and OFGs was examined. In addition, we constructed potential targeted drugs for this model through the Drug-Gene Interaction database (DGIdb) database. Finally, we verify the expression of S100A8-dominated OFGs in the GSE20681 dataset to confirm the universality of our study.ResultsWe identified the ten best OFGs for CAD from the DE-IRGs. Functional enrichment analysis showed that these marker genes are crucial for receptor-ligand activity, signaling receptor activator activity, and positive control of the response to stimuli from the outside world. Additionally, CIBERSORT revealed that S100A8 could be connected to alterations in the immune microenvironment in CAD patients. Furthermore, with the help of DGIdb and Cytoscape, a total of 64 medicines that target five marker genes were subsequently discovered. Finally, we verified the expression of the OFGs genes in the GSE20681 dataset between CAD patients and normal patients and found that there was also a significant difference in the expression of S100A8.ConclusionWe created a 10-gene immune-related prognostic model for CAD and confirmed its validity. The model can identify potential biomarkers for CAD prediction and more accurately gauge the progression of the disease.

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Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets.

Publications

Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets.

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