{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:28:41Z","timestamp":1790821721867,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T00:00:00Z","timestamp":1450137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["WIREs RNA"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>\n<jats:styled-content style=\"fixed-case\">MicroRNAs<\/jats:styled-content> have been discussed as non\u2010 or minimal invasive biomarkers with a remarkable extracellular stability. Despite a multitude of studies in basic research, there are only few independent validation studies on blood\u2010born <jats:styled-content style=\"fixed-case\">miRNAs<\/jats:styled-content> as disease markers. Toward clinical applications numerous obstacles still need to be overcome. They are of technical origin but also fundamentally associated with the source and the nature of <jats:styled-content style=\"fixed-case\">miRNAs<\/jats:styled-content>. Here, we emphasize on potential confounding factors, the nature and the source of <jats:styled-content style=\"fixed-case\">miRNAs<\/jats:styled-content>. We recently showed that age and gender could influence the pattern of circulating <jats:styled-content style=\"fixed-case\">miRNAs<\/jats:styled-content>. On the cellular level, the <jats:styled-content style=\"fixed-case\">miRNA<\/jats:styled-content> pattern differs between plasma and serum preparations. On the molecular level, one has to differentiate between extracellular <jats:styled-content style=\"fixed-case\">miRNAs<\/jats:styled-content> that are encapsulated in microvesicles or bound to proteins or high\u2010density lipoproteins. Using whole blood as source for <jats:styled-content style=\"fixed-case\">miRNAs<\/jats:styled-content> helps to minimize <jats:styled-content style=\"fixed-case\">miRNA<\/jats:styled-content> expression changes due to environmental influences and allows attributing <jats:styled-content style=\"fixed-case\">miRNA<\/jats:styled-content> changes to their cells of origin like B\u2010cells and T\u2010cells. Moreover, unambiguous annotation and differentiation from other noncoding <jats:styled-content style=\"fixed-case\">RNAs<\/jats:styled-content> can be challenging. Even not all <jats:styled-content style=\"fixed-case\">miRNAs<\/jats:styled-content> deposited in <jats:styled-content style=\"fixed-case\">miRBase<\/jats:styled-content> do necessarily represent true <jats:styled-content style=\"fixed-case\">miRNAs<\/jats:styled-content>, just a fraction of <jats:styled-content style=\"fixed-case\">miRNAs<\/jats:styled-content> in the reference database have been experimentally validated by Northern blotting. Functional evidence for a true <jats:styled-content style=\"fixed-case\">miRNA<\/jats:styled-content> should be obtained by cloning the precursor <jats:styled-content style=\"fixed-case\">miRNA<\/jats:styled-content> and by subsequent detection of the processed mature form in host cells. Surprisingly, attempts to finally confirm a true <jats:styled-content style=\"fixed-case\">miRNA<\/jats:styled-content> are frequently postponed until evidence has been established for a likely value as biomarker. <jats:italic>WIREs RNA<\/jats:italic> 2016, 7:148\u2013156. doi: 10.1002\/wrna.1320<\/jats:p><jats:p>This article is categorized under:\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>RNA in Disease and Development &gt; RNA in Disease<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1002\/wrna.1320","type":"journal-article","created":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T03:05:55Z","timestamp":1450235155000},"page":"148-156","source":"Crossref","is-referenced-by-count":74,"title":["Can circulating <scp>miRNAs<\/scp> live up to the promise of being minimal invasive biomarkers in clinical settings?"],"prefix":"10.1002","volume":"7","author":[{"given":"Andreas","family":"Keller","sequence":"first","affiliation":[{"name":"Chair for 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