Assessment of Circulating LncRNAs Under Physiologic and Pathologic Conditions in Humans Reveals Potential Limitations as Biomarkers

Long non-coding RNAs (lncRNA) are a new class of regulatory molecules with diverse cellular functions. Recent reports have suggested that extracellular lncRNAs are detectable in human plasma and may serve as biomarkers. Here, we sought to investigate circulating lncRNAs as potential biomarkers for p...

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Vydáno v:Scientific reports Ročník 6; číslo 1; s. 36596
Hlavní autoři: Schlosser, Kenny, Hanson, Jennifer, Villeneuve, Patrick J., Dimitroulakos, Jim, McIntyre, Lauralyn, Pilote, Louise, Stewart, Duncan J.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 18.11.2016
Nature Publishing Group
Témata:
38/90
631/337/384/2568
631/337/384/331
631/45/500
692/53/2421
692/699/75/593
Acute coronary syndromes
Biomarkers
Cardiovascular disease
Coronary artery
Heart diseases
Humanities and Social Sciences
Hypertension
multidisciplinary
Plasma
Pulmonary hypertension
Ribonucleic acid
RNA
Science
Septic shock
ISSN:2045-2322, 2045-2322
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Shrnutí:Long non-coding RNAs (lncRNA) are a new class of regulatory molecules with diverse cellular functions. Recent reports have suggested that extracellular lncRNAs are detectable in human plasma and may serve as biomarkers. Here, we sought to investigate circulating lncRNAs as potential biomarkers for pulmonary arterial hypertension (PAH). Eighty-four lncRNAs, representing some of the most abundant and functionally relevant candidates identified in cellular studies, were assessed via RT-qPCR in plasma from PAH and healthy subjects. However, despite preamplification, the majority of lncRNAs were surprisingly undetectable or sporadically detectable, and showed no differential changes. Systematic characterization of plasma/RNA quality and technical performance via internal and external controls revealed no evidence of RNA degradation or RT-qPCR inhibition, and most lncRNAs were robustly detectable in pulmonary tissue. In plasma, lncRNA levels were the lowest among several different RNA species examined, and this was generalizable to other chronic and acute vascular conditions including coronary artery disease, acute coronary syndrome, and septic shock. In addition, two of three previously reported circulating lncRNA biomarker candidates were not detectable in any of the plasma samples. This study reveals new insight on the relative levels of lncRNAs in circulation, which has important implications for their potential development as biomarkers.
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ISSN:2045-2322
2045-2322
DOI:10.1038/srep36596