Circular RNAs in Urine of Kidney Transplant Patients with Acute T Cell-Mediated Allograft Rejection

Abstract

BACKGROUND Circular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They are detectable in the blood of patients with acute kidney injury. We tested whether circRNAs were present in urine and could serve as new predictors of outcome in renal transplant patients with acute rejection. METHODS A global circRNA expression analysis using RNA from urine of patients with acute T cell-mediated renal allograft rejection and control transplant patients was performed. Dysregulated circRNAs were confirmed in a cohort of 62 patients with acute rejection, 10 patients after successful antirejection therapy, 18 control transplant patients without rejection, and 13 stable transplant patients with urinary tract infection. RESULTS A global screen revealed several circRNAs to be altered in urine of patients with acute rejection. Concentrations of 2 circRNAs including hsa_circ_0001334 and hsa_circ_0071475 were significantly increased. These were validated in the whole cohort of patients. hsa_circ_0001334 was upregulated in patients with acute rejection compared with controls. Concentrations of hsa_circ_0001334 normalized in patients with acute rejection following successful antirejection therapy. hsa_circ_0001334 was associated with higher decline in glomerular filtration rate 1 year after transplantation. CONCLUSIONS CircRNA concentrations are significantly dysregulated in patients with acute rejection at subclinical time points. Urinary hsa_circ_0001334 is a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function.

Charting extracellular transcriptomes in The Human Biofluid RNA Atlas

“…As a result, circRNAs are highly stable and have extended half-lives compared to linear mRNAs. 27 CircRNAs have been reported to be present in numerous human tissues 23 and in a few biofluids such as saliva 20 , blood 28 , semen 21 and urine 23,24 . A direct comparison of the circRNA read fraction between biofluids and tissues is currently lacking in literature.…”

“…As such, most studies have explored the abundance of individual mRNAs in one specific biofluid by RT-qPCR [13][14][15][16][17][18][19] . CircRNAs have been reported in saliva 20 , semen 21 , blood 22 and urine 23,24 . Recently, the mRNA content of plasma and serum has been investigated using dedicated sequencing approaches like Phospho-RNA-Seq and SILVERseq 25,26 .…”

<p>Construction of a circRNA-Related ceRNA Prognostic Regulatory Network in Breast Cancer</p>

“…NcRNAs are a novel type of RNA that is primarily expressed in eukaryotes and plays an essential role in maintaining regular physiological activity. [26][27][28][29][30] Although the ceRNA regulatory network has been widely verified, the circRNA-related ceRNA network has rarely been studied. In the current study, we established a circRNA-related ceRNA regulatory network and prognostic model in breast cancer by bioinformatic analysis.…”

Diagnostic, Prognostic, and Therapeutic Value of Non-Coding RNA Expression Profiles in Renal Transplantation

“…Regarding hsa_circ_0001334 and hsa_circ_0071475, the urinary expression of these circRNAs was significantly and specifically increased in patients with acute TCMR when compared to stable grafts without signs of rejection [65]. This finding was made by Kölling M et al, who performed a genome-wide analysis of circRNA expression in the urine of transplant patients with acute TCMR.…”