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Updated: Feb 5, 2026

Identification of Circular RNAs using RNA Sequencing
Published on: November 14, 2019
The Circular RNA
Malte Kölling1, Harald Seeger1, George Haddad1
1Division of Nephrology, University Hospital Zürich, Zürich, Switzerland.
Introduction:
Circular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They might have an impact on microRNA expression by their sponging activity. The detectability in blood of these RNA transcripts has been demonstrated in patients with cancer and cardiovascular disease. We tested the hypothesis that circulating circRNAs in blood of critically ill patients with acute kidney injury (AKI) at inception of renal replacement therapy may also be dysregulated and associated with patient survival.
Methods:
We performed a global circRNA expression analysis using RNA isolated from blood of patients with AKI as well as controls. This global screen revealed several dysregulated circRNAs in patients with AKI. Most highly increased circRNA-array-based transcripts as well as expression of the circRNA target miR-126-5p were confirmed in blood of 109 patients with AKI, 30 age-matched healthy controls, 25 critically ill non-AKI patients, and 20 patients on maintenance hemodialysis by quantitative real-time polymerase chain reaction.
Results:
Circulating concentrations of 3 novel circRNAs were amplified in blood of patients with AKI and in controls. Circular RNA sponge of miR-126 (or ciRs-126) was most highly altered compared to healthy controls and disease controls (fold change of 52.1). ciRs-126 was shown to bioinformatically sponge miR-126-5p, which was found to be highly suppressed in AKI patients and hypoxic endothelial cells. Cox regression and Kaplan-Meier curve analysis revealed ciRs-126 as an independent predictor of 28-day survival (P < 0.01).
Conclusion:
Circulating concentrations of circRNAs in patients with AKI are detectable. ciRs-126 may potentially sponge miR-126-5p and acts as a predictor of mortality in this patient cohort.
Insights
Circulating circular RNAs (circRNAs) are detectable in critically ill patients with acute kidney injury (AKI). A specific circRNA, ciRs-126, may predict mortality in AKI patients.
Area of Science:
- Molecular Biology
- Genomics
- Biochemistry
Background:
- Circular RNAs (circRNAs) are novel noncoding RNA regulators with potential roles in microRNA (miRNA) expression.
- circRNAs are detectable in blood and have been implicated in cancer and cardiovascular diseases.
- The presence and role of circRNAs in acute kidney injury (AKI) remain largely unexplored.
Purpose of the Study:
- To investigate the dysregulation and potential role of circulating circRNAs in critically ill patients with AKI.
- To determine if circulating circRNAs are associated with patient survival in AKI.
Main Methods:
- Global circRNA expression analysis was performed on blood samples from AKI patients and controls.
- Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate key circRNAs and their targets in a larger cohort.
- Statistical analyses, including Cox regression and Kaplan-Meier curves, were employed to assess survival prediction.
Main Results:
- Three novel circRNAs were found to be upregulated in the blood of AKI patients.
- Circular RNA sponge of miR-126 (ciRs-126) showed a significant 52.1-fold increase in AKI patients compared to controls.
- ciRs-126 was identified as a potential sponge for miR-126-5p, which was suppressed in AKI patients and hypoxic cells.
Conclusions:
- Circulating circRNAs are detectable in patients with AKI.
- ciRs-126 may function as a miRNA sponge for miR-126-5p.
- ciRs-126 is an independent predictor of 28-day mortality in AKI patients.
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