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. 2017 Nov;95(11):1179-1189.
doi: 10.1007/s00109-017-1582-9. Epub 2017 Aug 25.

A Map of Human Circular RNAs in Clinically Relevant Tissues

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Free PMC article

A Map of Human Circular RNAs in Clinically Relevant Tissues

Philipp G Maass et al. J Mol Med (Berl). .
Free PMC article

Abstract

Cellular circular RNAs (circRNAs) are generated by head-to-tail splicing and are present in all multicellular organisms studied so far. Recently, circRNAs have emerged as a large class of RNA which can function as post-transcriptional regulators. It has also been shown that many circRNAs are tissue- and stage-specifically expressed. Moreover, the unusual stability and expression specificity make circRNAs important candidates for clinical biomarker research. Here, we present a circRNA expression resource of 20 human tissues highly relevant to disease-related research: vascular smooth muscle cells (VSMCs), human umbilical vein cells (HUVECs), artery endothelial cells (HUAECs), atrium, vena cava, neutrophils, platelets, cerebral cortex, placenta, and samples from mesenchymal stem cell differentiation. In eight different samples from a single donor, we found highly tissue-specific circRNA expression. Circular-to-linear RNA ratios revealed that many circRNAs were expressed higher than their linear host transcripts. Among the 71 validated circRNAs, we noticed potential biomarkers. In adenosine deaminase-deficient, severe combined immunodeficiency (ADA-SCID) patients and in Wiskott-Aldrich-Syndrome (WAS) patients' samples, we found evidence for differential circRNA expression of genes that are involved in the molecular pathogenesis of both phenotypes. Our findings underscore the need to assess circRNAs in mechanisms of human disease. KEY MESSAGES: circRNA resource catalog of 20 clinically relevant tissues. circRNA expression is highly tissue-specific. circRNA transcripts are often more abundant than their linear host RNAs. circRNAs can be differentially expressed in disease-associated genes.

Keywords: Circular RNAs; Human cell types; Potential biomarker; circRNA catalog.

Conflict of interest statement

The authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
CircRNA expression in clinically relevant human tissues. a CircRNA catalog of human samples with total, new, and unique circRNAs. Samples in bold were derived from one donor. b Distribution of host gene annotation with potential circRNAs. c Differentially expressed top 10% circRNAs in hierarchical clustering. d CircRNAs from different clusters (C) were validated by qRT-PCR of RNase R-treated samples
Fig. 2
Fig. 2
CircRNAs are tissue-specific, highly abundant, and the expression can be differential in disease-associated genes. a Clustering of top 10% differentially expressed circRNAs in umbilical cord, EPCs, HUVECs, and HUAECs and b their validation. c Tissue-specific expression pattern reflected the overlaps of circRNAs in plasma, serum, neutrophils, and platelets and d their validation. e Circular-to-linear expression ratios revealed highly expressed circRNAs with multiple isoforms. f Validation of circRNAs from disease-relevant genes (GAPDH; Vinculin—linear negative control; hsa-circRNA-5—positive control). g CircRNA quantification in three different WAS and four ADA-SCID patients (AFF). The candidates were higher expressed in disease samples than in four controls (bars: mean expression ± SEM, two technical replicates per WAS or ADA-SCID patient group, except circCDC42BPA: controls n = 6, WAS n = 5, Student’s T test across samples and replicates, ***p < 0.001, **p < 0.01, *p < 0.05)

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