The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute Kidney Injury

Abstract

IntroductionCircular 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.MethodsWe 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.ResultsCirculating 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).ConclusionCirculating 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.

Circular RNA YAP1 acts as the sponge of microRNA‐21‐5p to secure HK‐2 cells from ischaemia/reperfusion‐induced injury

“…Among these, the levels of hsa_circ_0045881 and hsa_circ_0001177 were obviously enhanced in whole blood of AKI patients. Additionally, an association between ciRs‐126 and curve value was disclosed . Moreover, the decreased expression of circ‐Akt3 in AKI rat model might be closely related to immune response and inflammatory damage .…”

“…Researches analysing circRNA expression in AKI have described the dysregulated expression of nearly 50 circRNAs using genome‐wide expression analysis, compared to healthy cases . Among these, the levels of hsa_circ_0045881 and hsa_circ_0001177 were obviously enhanced in whole blood of AKI patients.…”

“…Recent research proved that the advantageous effects of circRNAs in AKI might be linked with their abnormal expression . Up to date, the up‐expression of circRNA ciRs‐126 was confirmed in AKI patients; meanwhile, ciRs‐126 was hopefully regarded as a biomarker to predict survival rate of AKI patients . It was proved that circRNA of Yes‐associated protein 1 (circYAP1, is also named as hsa_circ_0024093), a newly discovered type of circRNA, was down‐expressed in gastric cancer tissues and could attenuate cell proliferation and invasion of gastric cancer cells .…”

Hsa_circ_0123190 acts as a competitive endogenous RNA to regulate APLNR expression by sponging hsa-miR-483-3p in lupus nephritis

“…CircRNA is a special class of endogenous RNAs with multiple functions [18]. Many studies have revealed the abnormal circRNAs were associated with several renal diseases ,such as AKI [19], carcinoma [8,20]. However, the role of circRNA in LN was rarely reported.…”

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

“…CircRNAs also act as miRNA sponges and possess scaffolding functions that affect protein-protein interactions [21,22]. Although the expression and functional role of circRNAs in the kidney remains mostly unknown, some studies have postulated circRNAs as potential therapeutic targets in renal diseases [23,24].…”