Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

Abstract

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

Study on the Mechanism of circRNA Regulating the miRNA Level in Nephrotic Syndrome

“…Finally, we have identified several circRNAs that may associate with nephrotic syndrome, their downregulated expression in patients will lead to the upregulation of their targeting miRNAs, inducing targeting mRNAs to be upregulated and then generate the nephrotic syndrome. The mechanisms by which these circRNAs interact with miRNAs and mRNAs are unclear, but these circRNAs may be potential targets for the treatment of kidney disease, in line with the findings of Yu et al that circRNAs are novel diagnostic biomarkers and therapeutic targets for kidney disease [ 38 ], but whether these circRNAs can be biomarkers for nephrotic syndromes requires further testing.…”

Integrated Analysis of the CircRNA-Based ceRNA Network in Renal Fibrosis Induced by Ischemia Reperfusion Injury

“…CircRNA is fine-tuned and controlled in many physiological and pathological conditions, and could trigger a significant breakthrough in CKD prevention. Mounting evidence has shown that circRNA expression is altered in kidney disorders ( van Zonneveld et al, 2021 ; Yu et al, 2021 ). However, the identification and function of circRNAs are largely unknown in the context of renal fibrosis.…”

Structural Modifications of siRNA Improve Its Performance In Vivo

“…Circular RNAs (circRNA) are endogenous regulatory single-stranded, covalently closed RNA molecules that have recently attracted the attention of researchers studying their involvement in disease development as markers and potential molecular targets [ 49 , 50 , 51 ]. Recently, analogues of these natural RNAs have been proposed as synthetic inducers of RNAi—circular small interfering RNAs (csiRNAs).…”