Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease

Cell Metabolism - Tập 30 Số 4 - Trang 656-673 - 2019
Marcelo A. Mori1, Raissa G. Ludwig1, Rubén García-Martín2, Bruna B. Brandão2, C. Ronald Kahn2
1Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil
2Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA

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Al-Muhtaresh, 2018, Evaluation of two-diabetes related microRNAs suitability as earlier blood biomarkers for detecting prediabetes and type 2 diabetes mellitus, J. Clin. Med., 7

Ameling, 2015, Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study, BMC Med. Genomics, 8, 61, 10.1186/s12920-015-0136-7

Anfossi, 2018, Clinical utility of circulating non-coding RNAs - an update, Nat. Rev. Clin. Oncol., 15, 541, 10.1038/s41571-018-0035-x

Arner, 2012, Adipose tissue microRNAs as regulators of CCL2 production in human obesity, Diabetes, 61, 1986, 10.2337/db11-1508

Arner, 2015, MicroRNA regulatory networks in human adipose tissue and obesity, Nat. Rev. Endocrinol., 11, 276, 10.1038/nrendo.2015.25

Arroyo, 2011, Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma, Proc. Natl. Acad. Sci. USA, 108, 5003, 10.1073/pnas.1019055108

Bai, 2017, Downregulation of blood serum microRNA 29 family in patients with Parkinson's disease, Sci. Rep., 7, 5411, 10.1038/s41598-017-03887-3

Bandiera, 2015, miR-122–a key factor and therapeutic target in liver disease, J. Hepatol., 62, 448, 10.1016/j.jhep.2014.10.004

Bartel, 2018, Metazoan microRNAs, Cell, 173, 20, 10.1016/j.cell.2018.03.006

Beatty, 2014, Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma, BMC Genomics, 15, 933, 10.1186/1471-2164-15-933

Berezikov, 2011, Evolution of microRNA diversity and regulation in animals, Nat. Rev. Genet., 12, 846, 10.1038/nrg3079

Blanchard, 2002, TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex, J. Immunol., 168, 3235, 10.4049/jimmunol.168.7.3235

Bobrie, 2012, Diverse subpopulations of vesicles secreted by different intracellular mechanisms are present in exosome preparations obtained by differential ultracentrifugation, J. Extracell. Vesicles, 1

Booth, 2006, Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane, J. Cell Biol., 172, 923, 10.1083/jcb.200508014

Botta-Orfila, 2014, Identification of blood serum micro-RNAs associated with idiopathic and LRRK2 Parkinson's disease, J. Neurosci. Res., 92, 1071, 10.1002/jnr.23377

Brestoff, 2015, Immune regulation of metabolic homeostasis in health and disease, Cell, 161, 146, 10.1016/j.cell.2015.02.022

Bryant, 2012, Changes in circulating microRNA levels associated with prostate cancer, Br. J. Cancer, 106, 768, 10.1038/bjc.2011.595

Busatto, 2018, Tangential flow filtration for highly efficient concentration of extracellular vesicles from large volumes of fluid, Cells, 7, 10.3390/cells7120273

Campello, 2016, Dynamics of circulating microparticles in obesity after weight loss, Intern. Emerg. Med., 11, 695, 10.1007/s11739-016-1397-7

Can, 2016, The investigation of circulating microRNAs associated with lipid metabolism in childhood obesity, Pediatr. Obes., 11, 228, 10.1111/ijpo.12050

Cao, 2014, Adipocytokines in obesity and metabolic disease, J. Endocrinol., 220, T47, 10.1530/JOE-13-0339

Cao, 2008, Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism, Cell, 134, 933, 10.1016/j.cell.2008.07.048

Caravia, 2018, The microRNA-29/PGC1alpha regulatory axis is critical for metabolic control of cardiac function, PLoS Biol., 16, e2006247, 10.1371/journal.pbio.2006247

Caspi, 2007, Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts, J. Am. Coll. Cardiol., 50, 1884, 10.1016/j.jacc.2007.07.054

Castaño, 2018, Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice, Proc. Natl. Acad. Sci. USA, 115, 12158, 10.1073/pnas.1808855115

Castoldi, 2015, The macrophage switch in obesity development, Front. Immunol., 6, 637

Ceolotto, 2017, miR-30c-5p regulates macrophage-mediated inflammation and pro-atherosclerosis pathways, Cardiovasc. Res., 113, 1627, 10.1093/cvr/cvx157

Chartoumpekis, 2012, Differential expression of microRNAs in adipose tissue after long-term high-fat diet-induced obesity in mice, PLoS One, 7, e34872, 10.1371/journal.pone.0034872

Cheloufi, 2010, A dicer-independent miRNA biogenesis pathway that requires Ago catalysis, Nature, 465, 584, 10.1038/nature09092

Chen, 2008, Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure, Proc. Natl. Acad. Sci. USA, 105, 2111, 10.1073/pnas.0710228105

Chen, 2015, MiR-320a contributes to atherogenesis by augmenting multiple risk factors and down-regulating SRF, J. Cell. Mol. Med., 19, 970, 10.1111/jcmm.12483

Chen, 2016, Elucidation of exosome migration across the blood-brain barrier model in vitro, Cell. Mol. Bioeng., 9, 509, 10.1007/s12195-016-0458-3

Chen, 2017, MiR-126 affects brain-heart interaction after cerebral ischemic stroke, Transl. Stroke Res., 8, 374, 10.1007/s12975-017-0520-z

Cheng, 2015, Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment, Mol. Psychiatry, 20, 1188, 10.1038/mp.2014.127

Chevillet, 2014, Quantitative and stoichiometric analysis of the microRNA content of exosomes, Proc. Natl. Acad. Sci. USA, 111, 14888, 10.1073/pnas.1408301111

Choi, 2017, Adipose crosstalk with other cell types in health and disease, Exp. Cell Res., 360, 6, 10.1016/j.yexcr.2017.04.022

Chong, 2014, Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts, Nature, 510, 273, 10.1038/nature13233

Chuang, 2015, MicroRNA-223 expression is upregulated in insulin resistant human adipose tissue, J. Diabetes Res., 2015, 943659

Cocucci, 2015, Ectosomes and exosomes: shedding the confusion between extracellular vesicles, Trends Cell Biol., 25, 364, 10.1016/j.tcb.2015.01.004

Crewe, 2018, An endothelial-to-adipocyte extracellular vesicle axis governed by metabolic state, Cell, 175, 695, 10.1016/j.cell.2018.09.005

Das, 2019, The Extracellular RNA Communication Consortium: establishing foundational knowledge and technologies for extracellular RNA research, Cell, 177, 231, 10.1016/j.cell.2019.03.023

de Couto, 2017, Exosomal microRNA transfer Into macrophages mediates cellular postconditioning, Circulation, 136, 200, 10.1161/CIRCULATIONAHA.116.024590

de Lencastre, 2010, MicroRNAs both promote and antagonize longevity in C. elegans, Curr. Biol., 20, 2159, 10.1016/j.cub.2010.11.015

De Silva, 2018, Effects of exosomes from LPS-activated macrophages on adipocyte gene expression, differentiation, and insulin-dependent glucose uptake, J. Physiol. Biochem., 74, 559, 10.1007/s13105-018-0622-4

Deline, 2018, Evolution of metazoan morphological disparity, Proc. Natl. Acad. Sci. USA, 115, E8909, 10.1073/pnas.1810575115

Deng, 2009, Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance, Diabetes, 58, 2498, 10.2337/db09-0216

Dhahbi, 2013, Deep sequencing identifies circulating mouse miRNAs that are functionally implicated in manifestations of aging and responsive to calorie restriction, Aging, 5, 130, 10.18632/aging.100540

Dohm, 2008, Substantial biases in ultra-short read data sets from high-throughput DNA sequencing, Nucleic Acids Res., 36, e105, 10.1093/nar/gkn425

Dong, 2016, A panel of four decreased serum microRNAs as a novel biomarker for early Parkinson's disease, Biomarkers, 21, 129, 10.3109/1354750X.2015.1118544

Du, 2014, miR-17 extends mouse lifespan by inhibiting senescence signaling mediated by MKP7, Cell Death Dis., 5, e1355, 10.1038/cddis.2014.305

El Ouaamari, 2008, miR-375 targets 3′-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells, Diabetes, 57, 2708, 10.2337/db07-1614

Esau, 2006, miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting, Cell Metab., 3, 87, 10.1016/j.cmet.2006.01.005

Fendler, 2016, The translational potential of microRNAs as biofluid markers of urological tumours, Nat. Rev. Urol., 13, 734, 10.1038/nrurol.2016.193

Ferrante, 2015, Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease, Pediatr. Res., 77, 447, 10.1038/pr.2014.202

Fichtlscherer, 2010, Circulating microRNAs in patients with coronary artery disease, Circ. Res., 107, 677, 10.1161/CIRCRESAHA.109.215566

Fitzner, 2011, Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis, J. Cell Sci., 124, 447, 10.1242/jcs.074088

Flaherty, 2019, A lipase-independent pathway of lipid release and immune modulation by adipocytes, Science, 363, 989, 10.1126/science.aaw2586

Flowers, 2015, MicroRNAs associated with exercise and diet: a systematic review, Physiol. Genomics, 47, 1, 10.1152/physiolgenomics.00095.2014

Franceschi, 2018, Inflammaging: a new immune-metabolic viewpoint for age-related diseases, Nat. Rev. Endocrinol., 14, 576, 10.1038/s41574-018-0059-4

Galimberti, 2014, Circulating miRNAs as potential biomarkers in Alzheimer's disease, J. Alzheimers Dis., 42, 1261, 10.3233/JAD-140756

Gibbings, 2009, Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity, Nat. Cell Biol., 11, 1143, 10.1038/ncb1929

Glass, 2012, Inflammation and lipid signaling in the etiology of insulin resistance, Cell Metab., 15, 635, 10.1016/j.cmet.2012.04.001

Goren, 2012, Serum levels of microRNAs in patients with heart failure, Eur. J. Heart Fail., 14, 147, 10.1093/eurjhf/hfr155

Grasedieck, 2012, Impact of serum storage conditions on microRNA stability, Leukemia, 26, 2414, 10.1038/leu.2012.106

Guay, 2019, Lymphocyte-derived exosomal microRNAs promote pancreatic beta cell death and may contribute to type 1 diabetes development, Cell Metab., 29, 348, 10.1016/j.cmet.2018.09.011

Ha, 2014, Regulation of microRNA biogenesis, Nat. Rev. Mol. Cell Biol., 15, 509, 10.1038/nrm3838

Haneklaus, 2012, Cutting edge: miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1beta production, J. Immunol., 189, 3795, 10.4049/jimmunol.1200312

Hansen, 2010, Biases in Illumina transcriptome sequencing caused by random hexamer priming, Nucleic Acids Res., 38, e131, 10.1093/nar/gkq224

Haraszti, 2018, Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity, Mol. Ther., 26, 2838, 10.1016/j.ymthe.2018.09.015

He, 2015, Current state of circulating microRNAs as cancer biomarkers, Clin. Chem., 61, 1138, 10.1373/clinchem.2015.241190

He, 2018, Endothelial extracellular vesicles modulate the macrophage phenotype: potential implications in atherosclerosis, Scand. J. Immunol., 87, e12648, 10.1111/sji.12648

Heneghan, 2011, Differential miRNA expression in omental adipose tissue and in the circulation of obese patients identifies novel metabolic biomarkers, J. Clin. Endocrinol. Metab., 96, E846, 10.1210/jc.2010-2701

Higuchi, 2015, Identification of circulating miR-101, miR-375 and miR-802 as biomarkers for type 2 diabetes, Metab. Clin. Exp., 64, 489, 10.1016/j.metabol.2014.12.003

Holland, 2011, Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin, Nat. Med., 17, 55, 10.1038/nm.2277

Hong, 2017, Identification of circulating miR-125b as a potential biomarker of Alzheimer's disease in APP/PS1 transgenic mouse, J. Alzheimers Dis., 59, 1449, 10.3233/JAD-170156

Horak, 2016, Muscle-specific microRNAs in skeletal muscle development, Dev. Biol., 410, 1, 10.1016/j.ydbio.2015.12.013

Horibe, 2018, Mechanism of recipient cell-dependent differences in exosome uptake, BMC Cancer, 18, 47, 10.1186/s12885-017-3958-1

Hotamisligil, 2017, Inflammation, metaflammation and immunometabolic disorders, Nature, 542, 177, 10.1038/nature21363

Houbaviy, 2003, Embryonic stem cell-specific microRNAs, Dev. Cell, 5, 351, 10.1016/S1534-5807(03)00227-2

Hsieh, 2015, Weight-reduction through a low-fat diet causes differential expression of circulating microRNAs in obese C57BL/6 mice, BMC Genomics, 16, 699, 10.1186/s12864-015-1896-3

Huang, 2014, Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury, BMC Nephrol., 15, 142, 10.1186/1471-2369-15-142

Huang, 2018, Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons, FASEB J., 32, 512, 10.1096/fj.201700673r

Hubal, 2017, Circulating adipocyte-derived exosomal microRNAs associated with decreased insulin resistance after gastric bypass, Obesity, 25, 102, 10.1002/oby.21709

Huggett, 2013, The digital MIQE guidelines: minimum Information for publication of quantitative digital PCR experiments, Clin. Chem., 59, 892, 10.1373/clinchem.2013.206375

Ibáñez-Ventoso, 2006, Modulated microRNA expression during adult lifespan in Caenorhabditis elegans, Aging Cell, 5, 235, 10.1111/j.1474-9726.2006.00210.x

Ismail, 2013, Macrophage microvesicles induce macrophage differentiation and miR-223 transfer, Blood, 121, 984, 10.1182/blood-2011-08-374793

Jansen, 2014, MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease, J. Am. Heart Assoc., 3, e001249, 10.1161/JAHA.114.001249

Jeppesen, 2019, Reassessment of exosome composition, Cell, 177, 428, 10.1016/j.cell.2019.02.029

Jia, 2016, Downregulated serum miR-223 servers as biomarker in Alzheimer's disease, Cell Biochem. Funct., 34, 233, 10.1002/cbf.3184

Jiang, 2014, Peripheral blood miRNAs as a biomarker for chronic cardiovascular diseases, Sci. Rep., 4, 5026, 10.1038/srep05026

Jones, 2017, miRNA signatures of insulin resistance in obesity, Obesity, 25, 1734, 10.1002/oby.21950

Jopling, 2012, Liver-specific microRNA-122: biogenesis and function, RNA Biol., 9, 137, 10.4161/rna.18827

Karolina, 2012, Circulating miRNA profiles in patients with metabolic syndrome, J. Clin. Endocrinol. Metab., 97, E2271, 10.1210/jc.2012-1996

Katayama, 2019, Circulating exosomal miR-20b-5p is elevated in type 2 diabetes and could impair insulin action in human skeletal muscle, Diabetes, 68, 515, 10.2337/db18-0470

Kawase-Koga, 2009, Different timings of Dicer deletion affect neurogenesis and gliogenesis in the developing mouse central nervous system, Dev. Dyn., 238, 2800, 10.1002/dvdy.22109

Keller, 2017, Improved risk stratification in prevention by use of a panel of selected circulating microRNAs, Sci. Rep., 7, 4511, 10.1038/s41598-017-04040-w

Khan, 2015, Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction, Circ. Res., 117, 52, 10.1161/CIRCRESAHA.117.305990

Kim, 2014, MicroRNAs are required for the feature maintenance and differentiation of brown adipocytes, Diabetes, 63, 4045, 10.2337/db14-0466

Kirkman, 2012, Diabetes in older adults, Diabetes Care, 35, 2650, 10.2337/dc12-1801

Kloosterman, 2007, Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development, PLoS Biol., 5, e203, 10.1371/journal.pbio.0050203

Klöting, 2009, MicroRNA expression in human omental and subcutaneous adipose tissue, PLoS One, 4, e4699, 10.1371/journal.pone.0004699

Koeck, 2014, Adipocyte exosomes induce transforming growth factor beta pathway dysregulation in hepatocytes: a novel paradigm for obesity-related liver disease, J. Surg. Res., 192, 268, 10.1016/j.jss.2014.06.050

Kong, 2011, Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study, Acta Diabetol., 48, 61, 10.1007/s00592-010-0226-0

Kopecki, 2007, Collagen loss and impaired wound healing is associated with c-Myb deficiency, J. Pathol., 211, 351, 10.1002/path.2113

Kovacs, 2011, MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats, Invest. Ophthalmol. Vis. Sci., 52, 4402, 10.1167/iovs.10-6879

Krützfeldt, 2005, Silencing of microRNAs in vivo with 'antagomirs', Nature, 438, 685, 10.1038/nature04303

Kumar, 2013, Circulating miRNA biomarkers for Alzheimer's disease, PLoS One, 8, e69807, 10.1371/journal.pone.0069807

Lackey, 2016, Regulation of metabolism by the innate immune system, Nat. Rev. Endocrinol., 12, 15, 10.1038/nrendo.2015.189

Lagos-Quintana, 2002, Identification of tissue-specific microRNAs from mouse, Curr. Biol., 12, 735, 10.1016/S0960-9822(02)00809-6

Lahmy, 2014, MiRNA-375 promotes beta pancreatic differentiation in human induced pluripotent stem (hiPS) cells, Mol. Biol. Rep., 41, 2055, 10.1007/s11033-014-3054-4

Lai, 2014, Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter, ACS Nano, 8, 483, 10.1021/nn404945r

Latreille, 2015, miR-375 gene dosage in pancreatic beta-cells: implications for regulation of beta-cell mass and biomarker development, J. Mol. Med., 93, 1159, 10.1007/s00109-015-1296-9

Leidinger, 2013, A blood based 12-miRNA signature of Alzheimer disease patients, Genome Biol., 14, R78, 10.1186/gb-2013-14-7-r78

Li, 2010, MicroRNAs modulate the noncanonical transcription factor NF-kappaB pathway by regulating expression of the kinase IKKalpha during macrophage differentiation, Nat. Immunol., 11, 799, 10.1038/ni.1918

Li, 2011, Up-regulation of key microRNAs, and inverse down-regulation of their predicted oxidative phosphorylation target genes, during aging in mouse brain, Neurobiol. Aging, 32, 944, 10.1016/j.neurobiolaging.2009.04.020

Li, 2016, Cell-derived microparticles in patients with type 2 diabetes mellitus: a systematic review and meta-analysis, Cell. Physiol. Biochem., 39, 2439, 10.1159/000452512

Liang, 2018, Identification of stress-related microRNA biomarkers in type 2 diabetes mellitus: a systematic review and meta-analysis, J. Diabetes

Lin, 2016, MiR-155 enhances insulin sensitivity by coordinated regulation of multiple genes in mice, PLoS Genet., 12, e1006308, 10.1371/journal.pgen.1006308

Ling, 2013, Modulation of microRNAs in hypertension-induced arterial remodeling through the beta1 and beta3-adrenoreceptor pathways, J. Mol. Cell. Cardiol., 65, 127, 10.1016/j.yjmcc.2013.10.003

Liu, 2016, Pathogenesis of nonalcoholic steatohepatitis, Cell. Mol. Life Sci., 73, 1969, 10.1007/s00018-016-2161-x

López-Otín, 2013, The hallmarks of aging, Cell, 153, 1194, 10.1016/j.cell.2013.05.039

Lu, 2010, MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism, Cardiovasc. Res., 86, 410, 10.1093/cvr/cvq010

Ludwig, 2016, Distribution of miRNA expression across human tissues, Nucleic Acids Res., 44, 3865, 10.1093/nar/gkw116

Lugli, 2015, Plasma exosomal miRNAs in persons with and without Alzheimer disease: altered expression and prospects for biomarkers, PLoS One, 10, e0139233, 10.1371/journal.pone.0139233

Lynes, 2017, The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue, Nat. Med., 23, 631, 10.1038/nm.4297

Lynn, 2007, MicroRNA expression is required for pancreatic islet cell genesis in the mouse, Diabetes, 56, 2938, 10.2337/db07-0175

Ma, 2016, Serum miR-221 serves as a biomarker for Parkinson's disease, Cell Biochem. Funct., 34, 511, 10.1002/cbf.3224

Machida, 2015, MicroRNAs in salivary exosome as potential biomarkers of aging, Int. J. Mol. Sci., 16, 21294, 10.3390/ijms160921294

Maes, 2008, Murine microRNAs implicated in liver functions and aging process, Mech. Ageing Dev., 129, 534, 10.1016/j.mad.2008.05.004

Margis, 2011, Identification of blood microRNAs associated to Parkinson’s disease, J. Biotechnol., 152, 96, 10.1016/j.jbiotec.2011.01.023

Marson, 2008, Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells, Cell, 134, 521, 10.1016/j.cell.2008.07.020

Mateescu, 2017, Obstacles and opportunities in the functional analysis of extracellular vesicle RNA - an ISEV position paper, J. Extracell. Vesicles, 6, 1286095, 10.1080/20013078.2017.1286095

Mathieu, 2019, Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication, Nat. Cell Biol., 21, 9, 10.1038/s41556-018-0250-9

Mathis, 2013, Immunological goings-on in visceral adipose tissue, Cell Metab., 17, 851, 10.1016/j.cmet.2013.05.008

Matsumoto, 2017, The transport mechanism of extracellular vesicles at the blood-brain barrier, Curr. Pharm. Des., 23, 6206, 10.2174/1381612823666170913164738

McKelvey, 2015, Exosomes: mechanisms of uptake, J. Circ. Biomarkers, 4, 7, 10.5772/61186

McKenzie, 2016, KRAS-MEK signaling controls Ago2 sorting into exosomes, Cell Rep., 15, 978, 10.1016/j.celrep.2016.03.085

Meerson, 2013, Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism downstream of leptin and TNF-alpha, Diabetologia, 56, 1971, 10.1007/s00125-013-2950-9

Melo, 2014, Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis, Cancer Cell, 26, 707, 10.1016/j.ccell.2014.09.005

Mitchell, 2008, Circulating microRNAs as stable blood-based markers for cancer detection, Proc. Natl. Acad. Sci. USA, 105, 10513, 10.1073/pnas.0804549105

Mittelbrunn, 2011, Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells, Nat. Commun., 2, 282, 10.1038/ncomms1285

Mocharla, 2013, AngiomiR-126 expression and secretion from circulating CD34+ and CD14+ PBMCs: role for pro-angiogenic effects and alterations in type-2 diabetics, Blood, 121, 226, 10.1182/blood-2012-01-407106

Mori, 2010, A systems biology approach identifies inflammatory abnormalities between mouse strains prior to development of metabolic disease, Diabetes, 59, 2960, 10.2337/db10-0367

Mori, 2012, Role of microRNA processing in adipose tissue in stress defense and longevity, Cell Metab., 16, 336, 10.1016/j.cmet.2012.07.017

Mori, 2014, Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy, J. Clin. Invest., 124, 3339, 10.1172/JCI73468

Mulcahy, 2014, Routes and mechanisms of extracellular vesicle uptake, J. Extracell. Vesicles, 3

Müller, 2011, Microvesicles released from rat adipocytes and harboring glycosylphosphatidylinositol-anchored proteins transfer RNA stimulating lipid synthesis, Cell. Signal., 23, 1207, 10.1016/j.cellsig.2011.03.013

Murillo, 2019, exRNA atlas analysis reveals distinct extracellular RNA cargo types and their carriers present across human Biofluids, Cell, 177, 463, 10.1016/j.cell.2019.02.018

Nathan, 2015, MiR-375 promotes redifferentiation of adult human beta cells expanded in vitro, PLoS One, 10, e0122108, 10.1371/journal.pone.0122108

Nedaeinia, 2017, Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer, Cancer Gene Ther., 24, 48, 10.1038/cgt.2016.77

Nidadavolu, 2013, Identification of microRNAs dysregulated in cellular senescence driven by endogenous genotoxic stress, Aging, 5, 460, 10.18632/aging.100571

Noren Hooten, 2010, MicroRNA expression patterns reveal differential expression of target genes with age, PLoS One, 5, e10724, 10.1371/journal.pone.0010724

Noren Hooten, 2013, Age-related changes in microRNA levels in serum, Aging, 5, 725, 10.18632/aging.100603

Nunez Lopez, 2016, Altered levels of circulating cytokines and microRNAs in lean and obese individuals with prediabetes and type 2 diabetes, Mol. Biosyst., 13, 106, 10.1039/C6MB00596A

Odegaard, 2013, Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis, Science, 339, 172, 10.1126/science.1230721

Oliverio, 2016, Dicer1-miR-328-Bace1 signalling controls brown adipose tissue differentiation and function, Nat. Cell Biol., 18, 328, 10.1038/ncb3316

Olivieri, 2012, Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammaging, Mech. Ageing Dev., 133, 675, 10.1016/j.mad.2012.09.004

Olivieri, 2014, Age- and glycemia-related miR-126-3p levels in plasma and endothelial cells, Aging, 6, 771, 10.18632/aging.100693

Ono, 2018, Identification of microRNA that represses IRS-1 expression in liver, PLoS One, 13, e0191553, 10.1371/journal.pone.0191553

O'Rourke, 2007, Essential role for Dicer during skeletal muscle development, Dev. Biol., 311, 359, 10.1016/j.ydbio.2007.08.032

Ortega, 2010, miRNA expression profile of human subcutaneous adipose and during adipocyte differentiation, PLoS One, 5, e9022, 10.1371/journal.pone.0009022

Ortega, 2013, Targeting the circulating microRNA signature of obesity, Clin. Chem., 59, 781, 10.1373/clinchem.2012.195776

Ortega, 2014, Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization, Diabetes Care, 37, 1375, 10.2337/dc13-1847

Ortega, 2015, Inflammation triggers specific microRNA profiles in human adipocytes and macrophages and in their supernatants, Clin. Epigenet., 7, 49, 10.1186/s13148-015-0083-3

Ostrowski, 2010, Rab27a and Rab27b control different steps of the exosome secretion pathway, Nat. Cell Biol., 12, 19, 10.1038/ncb2000

Pescador, 2013, Serum circulating microRNA profiling for identification of potential type 2 diabetes and obesity biomarkers, PLoS One, 8, e77251, 10.1371/journal.pone.0077251

Pirola, 2015, Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis, Gut, 64, 800, 10.1136/gutjnl-2014-306996

Povero, 2014, Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease, PLoS One, 9, e113651, 10.1371/journal.pone.0113651

Poy, 2004, A pancreatic islet-specific microRNA regulates insulin secretion, Nature, 432, 226, 10.1038/nature03076

Prud'homme, 2016, Neuropilin-1 is a receptor for extracellular miRNA and AGO2/miRNA complexes and mediates the internalization of miRNAs that modulate cell function, Oncotarget, 7, 68057, 10.18632/oncotarget.10929

Pusic, 2014, Youth and environmental enrichment generate serum exosomes containing miR-219 that promote CNS myelination, Glia, 62, 284, 10.1002/glia.22606

Reis, 2016, Fat-specific dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice, Aging (Albany NY), 8, 1201

Rome, 2015, Use of miRNAs in biofluids as biomarkers in dietary and lifestyle intervention studies, Genes Nutr., 10, 483, 10.1007/s12263-015-0483-1

Rong, 2013, Increased microRNA-146a levels in plasma of patients with newly diagnosed type 2 diabetes mellitus, PLoS One, 8, e73272, 10.1371/journal.pone.0073272

Rosas-Hernandez, 2018, Identification of altered microRNAs in serum of a mouse model of Parkinson's disease, Neurosci. Lett., 687, 1, 10.1016/j.neulet.2018.07.022

Rozowsky, 2019, exceRpt: a comprehensive analytic platform for extracellular RNA profiling, Cell Syst, 8, 352, 10.1016/j.cels.2019.03.004

Safdar, 2016, The potential of endurance exercise-derived exosomes to treat metabolic diseases, Nat. Rev. Endocrinol., 12, 504, 10.1038/nrendo.2016.76

Safdar, 2018, Exosomes as mediators of the systemic adaptations to endurance exercise, Cold Spring Harb. Perspect. Med., 8, 10.1101/cshperspect.a029827

Santangelo, 2018, A microRNA signature from serum exosomes of patients with glioma as complementary diagnostic biomarker, J. Neurooncol., 136, 51, 10.1007/s11060-017-2639-x

Schulte, 2015, miRNA-197 and miRNA-223 predict cardiovascular death in a cohort of patients with symptomatic coronary artery disease, PLoS One, 10, e0145930, 10.1371/journal.pone.0145930

Sekine, 2009, Disruption of Dicer1 induces dysregulated fetal gene expression and promotes hepatocarcinogenesis, Gastroenterology, 136, 2304, 10.1053/j.gastro.2009.02.067

Shan, 2015, An endocrine genetic signal between blood cells and vascular smooth muscle cells: role of MicroRNA-223 in smooth muscle function and atherogenesis, J. Am. Coll. Cardiol., 65, 2526, 10.1016/j.jacc.2015.03.570

Shapouri-Moghaddam, 2018, Macrophage plasticity, polarization, and function in health and disease, J. Cell. Physiol., 233, 6425, 10.1002/jcp.26429

Shen, 2012, A steroid receptor-microRNA switch regulates life span in response to signals from the gonad, Science, 338, 1472, 10.1126/science.1228967

Shi, 2014, Differential expression of microRNAs in omental adipose tissue from gestational diabetes mellitus subjects reveals miR-222 as a regulator of ERalpha expression in estrogen-induced insulin resistance, Endocrinology, 155, 1982, 10.1210/en.2013-2046

Shurtleff, 2016, Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction, Elife, 5, 10.7554/eLife.19276

Shurtleff, 2018, Extracellular vesicles and cancer: caveat lector, Annu. Rev. Cancer Biol., 2, 395, 10.1146/annurev-cancerbio-030617-050519

Smith-Vikos, 2012, MicroRNAs and their roles in aging, J. Cell Sci., 125, 7, 10.1242/jcs.099200

Soh, 2013, MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion, Nat. Med., 19, 892, 10.1038/nm.3200

Sohn, 2015, Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma, Exp. Mol. Med., 47, e184, 10.1038/emm.2015.68

Squadrito, 2014, Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells, Cell Rep., 8, 1432, 10.1016/j.celrep.2014.07.035

Srinivasan, 2019, Small RNA sequencing across diverse biofluids identifies optimal methods for exRNA isolation, Cell, 177, 446, 10.1016/j.cell.2019.03.024

Stanford, 2018, 12,13-diHOME: an exercise-induced lipokine that increases skeletal muscle fatty acid uptake, Cell Metab, 27, 1111, 10.1016/j.cmet.2018.03.020

Stepanian, 2013, Microparticle increase in severe obesity: not related to metabolic syndrome and unchanged after massive weight loss, Obesity, 21, 2236, 10.1002/oby.20365

Stern, 2016, Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk, Cell Metab., 23, 770, 10.1016/j.cmet.2016.04.011

Sun, 2014, Expression and DNA methylation status of microRNA-375 in patients with type 2 diabetes mellitus, Mol. Med. Rep., 9, 967, 10.3892/mmr.2013.1872

Suzuki, 2015, Adipose tissue-derived stem cells as a therapeutic tool for cardiovascular disease, World J. Cardiol., 7, 454, 10.4330/wjc.v7.i8.454

Sweeney, 2018, Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders, Nat. Rev. Neurol., 14, 133, 10.1038/nrneurol.2017.188

Takahashi, 2013, Visualization and in vivo tracking of the exosomes of murine melanoma B16-BL6 cells in mice after intravenous injection, J. Biotechnol., 165, 77, 10.1016/j.jbiotec.2013.03.013

Tan, 2014, Genome-wide serum microRNA expression profiling identifies serum biomarkers for Alzheimer's disease, J. Alzheimers Dis., 40, 1017, 10.3233/JAD-132144

Tarver, 2015, MicroRNAs and the evolution of complex multicellularity: identification of a large, diverse complement of microRNAs in the brown alga Ectocarpus, Nucleic Acids Res., 43, 6384, 10.1093/nar/gkv578

Théry, 2018, Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines, J. Extracell. Vesicles, 7, 1535750, 10.1080/20013078.2018.1535750

Thomou, 2017, Adipose-derived circulating miRNAs regulate gene expression in other tissues, Nature, 542, 450, 10.1038/nature21365

Togliatto, 2016, Obesity reduces the pro-angiogenic potential of adipose tissue stem cell-derived extracellular vesicles (EVs) by impairing miR-126 content: impact on clinical applications, Int. J. Obes. (Lond.), 40, 102, 10.1038/ijo.2015.123

Torriani, 2016, Dysfunctional subcutaneous fat With reduced dicer and brown adipose tissue gene expression in HIV-infected patients, J. Clin. Endocrinol. Metab., 101, 1225, 10.1210/jc.2015-3993

Trajkovic, 2008, Ceramide triggers budding of exosome vesicles into multivesicular endosomes, Science, 319, 1244, 10.1126/science.1153124

Treiber, 2019, Regulation of microRNA biogenesis and its crosstalk with other cellular pathways, Nat. Rev. Mol. Cell Biol., 20, 5, 10.1038/s41580-018-0059-1

Turpin, 2014, Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance, Cell Metab., 20, 678, 10.1016/j.cmet.2014.08.002

Ungvari, 2013, Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells, J. Gerontol. A Biol. Sci. Med. Sci., 68, 877, 10.1093/gerona/gls242

Valadi, 2007, Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells, Nat. Cell Biol., 9, 654, 10.1038/ncb1596

Vallabhajosyula, 2017, Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue, J. Clin. Invest., 127, 1375, 10.1172/JCI87993

Van Deun, 2017, EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research, Nat. Methods, 14, 228, 10.1038/nmeth.4185

van Niel, 2018, Shedding light on the cell biology of extracellular vesicles, Nat. Rev. Mol. Cell Biol., 19, 213, 10.1038/nrm.2017.125

Vasudevan, 2007, Switching from repression to activation: microRNAs can up-regulate translation, Science, 318, 1931, 10.1126/science.1149460

Vickers, 2011, MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins, Nat. Cell Biol., 13, 423, 10.1038/ncb2210

Vickers, 2014, MicroRNA-223 coordinates cholesterol homeostasis, Proc. Natl. Acad. Sci. USA, 111, 14518, 10.1073/pnas.1215767111

Villard, 2015, Diagnostic value of cell-free circulating microRNAs for obesity and type 2 diabetes: a meta-analysis, J. Mol. Biomarkers Diagn., 6

Villarroya-Beltri, 2013, SUMOylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs, Nat. Commun., 4, 2980, 10.1038/ncomms3980

Wang, 2008, Embryonic stem cell-specific microRNAs regulate the G1-S transition and promote rapid proliferation, Nat. Genet., 40, 1478, 10.1038/ng.250

Wang, 2009, MicroRNA-320 expression in myocardial microvascular endothelial cells and its relationship with insulin-like growth factor-1 in type 2 diabetic rats, Clin. Exp. Pharmacol. Physiol., 36, 181, 10.1111/j.1440-1681.2008.05057.x

Wang, 2010, Export of microRNAs and microRNA-protective protein by mammalian cells, Nucleic Acids Res., 38, 7248, 10.1093/nar/gkq601

Wang, 2013, Circulating miR-130b mediates metabolic cross talk between fat and muscle in overweight, Diabetologia, 56, 2275, 10.1007/s00125-013-2996-8

Wang, 2014, Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells, J. Mol. Cell. Cardiol., 74, 139, 10.1016/j.yjmcc.2014.05.001

Wang, 2015, Elevated circulating microRNA-122 is associated with obesity and insulin resistance in young adults, Eur. J. Endocrinol., 172, 291, 10.1530/EJE-14-0867

Wang, 2018, Exosomes derived from miR-214-enriched bone marrow-derived mesenchymal stem cells regulate oxidative damage in cardiac stem cells by targeting CaMKII, Oxid. Med. Cell. Longev., 2018, 4971261, 10.1155/2018/4971261

Weber, 2010, The microRNA spectrum in 12 body fluids, Clin. Chem., 56, 1733, 10.1373/clinchem.2010.147405

Wen, 2015, Circulating microRNA-223 as a potential biomarker for obesity, Obes. Res. Clin. Pract., 9, 398, 10.1016/j.orcp.2015.01.006

Whitham, 2018, Extracellular vesicles provide a means for tissue crosstalk during exercise, Cell Metab., 27, 237, 10.1016/j.cmet.2017.12.001

Willeit, 2017, Circulating microRNA-122 is associated with the risk of new-onset metabolic syndrome and type 2 diabetes, Diabetes, 66, 347, 10.2337/db16-0731

Williams, 2013, Comprehensive profiling of circulating microRNA via small RNA sequencing of cDNA libraries reveals biomarker potential and limitations, Proc. Natl. Acad. Sci. USA, 110, 4255, 10.1073/pnas.1214046110

Wong, 2018, Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications, Nat. Rev. Gastroenterol. Hepatol., 15, 137, 10.1038/nrgastro.2017.169

Wu, 2015, Profiling peripheral microRNAs in obesity and type 2 diabetes mellitus, APMIS, 123, 580, 10.1111/apm.12389

Xia, 2011, Over-expression of miR375 reduces glucose-induced insulin secretion in Nit-1 cells, Mol. Biol. Rep., 38, 3061, 10.1007/s11033-010-9973-9

Xiao, 2007, MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb, Cell, 131, 146, 10.1016/j.cell.2007.07.021

Xiao, 2016, Cardiac progenitor cell-derived exosomes prevent cardiomyocytes apoptosis through exosomal miR-21 by targeting PDCD4, Cell Death Dis., 7, e2277, 10.1038/cddis.2016.181

Xie, 2009, MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity, Diabetes, 58, 1050, 10.2337/db08-1299

Yang, 2018, Exosomes secreted by adipose-derived stem cells contribute to angiogenesis of brain microvascular endothelial cells following oxygen-glucose deprivation in vitro through microRNA-181b/TRPM7 axis, J. Mol. Neurosci., 65, 74, 10.1007/s12031-018-1071-9

Ying, 2017, Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity, Cell, 171, 372, 10.1016/j.cell.2017.08.035

Yore, 2014, Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects, Cell, 159, 318, 10.1016/j.cell.2014.09.035

Yu, 2018, Adipocyte-derived exosomal MiR-27a induces insulin resistance in skeletal muscle Through repression of PPARγ, Theranostics, 8, 2171, 10.7150/thno.22565

Zagrean, 2018, Multicellular crosstalk between exosomes and the neurovascular unit after cerebral ischemia. Therapeutic implications, Front. Neurosci., 12, 811, 10.3389/fnins.2018.00811

Zaharie, 2015, Exosome-carried microRNA-375 inhibits cell progression and dissemination via Bcl-2 blocking in colon cancer, J. Gastrointest. Liver Dis., 24, 435, 10.15403/jgld.2014.1121.244.375

Zampetaki, 2010, Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes, Circ. Res., 107, 810, 10.1161/CIRCRESAHA.110.226357

Zampetaki, 2012, Prospective study on circulating microRNAs and risk of myocardial infarction, J. Am. Coll. Cardiol., 60, 290, 10.1016/j.jacc.2012.03.056

Zernecke, 2009, Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection, Sci. Signal., 2, ra81, 10.1126/scisignal.2000610

Zhang, 2010, Secreted monocytic miR-150 enhances targeted endothelial cell migration, Mol. Cell, 39, 133, 10.1016/j.molcel.2010.06.010

Zhang, 2014, MicroRNA directly enhances mitochondrial translation during muscle differentiation, Cell, 158, 607, 10.1016/j.cell.2014.05.047

Zhang, 2015, Investigation of microRNA expression in human serum during the aging process, J. Gerontol. A Biol. Sci. Med. Sci., 70, 102, 10.1093/gerona/glu145

Zhang, 2016, Adipocyte-derived microvesicles from obese mice induce M1 macrophage phenotype through secreted miR-155, J. Mol. Cell Biol., 8, 505, 10.1093/jmcb/mjw040

Zhang, 2017, Reduced circulating levels of miR-433 and miR-133b are potential biomarkers for Parkinson's disease, Front. Cell. Neurosci., 11, 170, 10.3389/fncel.2017.00170

Zhang, 2017, Hypothalamic stem cells control ageing speed partly through exosomal miRNAs, Nature, 548, 52, 10.1038/nature23282

Zhang, 2018, Islet β cell: an endocrine cell secreting miRNAs, Biochem. Biophys. Res. Commun., 495, 1648, 10.1016/j.bbrc.2017.12.028

Zhao, 2010, Up-regulated pancreatic tissue microRNA-375 associates with human type 2 diabetes through beta-cell deficit and islet amyloid deposition, Pancreas, 39, 843, 10.1097/MPA.0b013e3181d12613

Zhao, 2014, Serum microRNA-133b is associated with low ceruloplasmin levels in Parkinson's disease, Parkinsonism Relat. Disord., 20, 1177, 10.1016/j.parkreldis.2014.08.016

Zhao, 2018, Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissues, Diabetes, 67, 235, 10.2337/db17-0356

Zheng, 2011, Bias detection and correction in RNA-sequencing data, BMC Bioinformatics, 12, 290, 10.1186/1471-2105-12-290

Zheng, 2017, Exosome-mediated miR-155 transfer from smooth muscle cells to endothelial cells induces endothelial injury and promotes atherosclerosis, Mol. Ther., 25, 1279, 10.1016/j.ymthe.2017.03.031

Zhou, 2013, Regulation of vascular smooth muscle cell turnover by endothelial cell-secreted microRNA-126: role of shear stress, Circ. Res., 113, 40, 10.1161/CIRCRESAHA.113.280883

Zhu, 2015, Identification of microRNA biomarkers in type 2 diabetes: a meta-analysis of controlled profiling studies, Diabetologia, 58, 900, 10.1007/s00125-015-3510-2

Zhuang, 2012, Small RNA expression profiling by high-throughput sequencing: implications of enzymatic manipulation, J. Nucleic Acids, 2012, 360358

Zhuang, 2012, A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation, Circulation, 125, 2892, 10.1161/CIRCULATIONAHA.111.087817