circRNAs Signature as Potential Diagnostic and Prognostic Biomarker for Diabetes Mellitus and Related Cardiovascular Complications

Abstract

Circular RNAs (circRNAs) belong to the ever-growing class of naturally occurring noncoding RNAs (ncRNAs) molecules. Unlike linear RNA, circRNAs are covalently closed transcripts mostly generated from precursor-mRNA by a non-canonical event called back-splicing. They are highly stable, evolutionarily conserved, and widely distributed in eukaryotes. Some circRNAs are believed to fulfill a variety of functions inside the cell mainly by acting as microRNAs (miRNAs) or RNA-binding proteins (RBPs) sponges. Furthermore, mounting evidence suggests that the misregulation of circRNAs is among the first alterations in various metabolic disorders including obesity, hypertension, and cardiovascular diseases. More recent research has revealed that circRNAs also play a substantial role in the pathogenesis of diabetes mellitus (DM) and related vascular complications. These findings have added a new layer of complexity to our understanding of DM and underscored the need to reexamine the molecular pathways that lead to this disorder in the context of epigenetics and circRNA regulatory mechanisms. Here, I review current knowledge about circRNAs dysregulation in diabetes and describe their potential role as innovative biomarkers to predict diabetes-related cardiovascular (CV) events. Finally, I discuss some of the actual limitations to the promise of these RNA transcripts as emerging therapeutics and provide recommendations for future research on circRNA-based medicine.

Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus

“…Overexpression of some circRNAs was associated with the upregulation of ECM degrading enzymes and inhibition of matrix proteins such as type II collagen and aggrecan [122]. Dysregulation of circRNA was also observed in patients with DM and was primarily associated with regulation of insulin secretion by β-cells as well as vascular complications including diabetic nephropathy, neuropathy, and cardiomyopathy [118]. CircRNAs are also involved in the regulation of miRNA activity by the formation of miRNA sponges that interact with RNA-binding proteins (RBPs) to regulate gene transcription and protein translation [123].…”

“…e recent introduction of high-throughput sequencing has resulted in the identification of endogenous circular RNAs (circRNAs) derived from precursor mRNA in different tissues [118]. CircRNAs represent endogenous noncoding RNAs characterized by covalently closed cyclic structures with nonpolyadenylated tails, which function as translational regulators, RNA-binding sponges, and microRNA sponges [119].…”

Epigenetic modification and therapeutic targets of diabetes mellitus

“…VEGF, FZD4 and WNT2. This formed a new regulatory network consisting of circRNAs, miRNAs and mRNAs that plays an important role in diabetic retinal vascular dysfunction [ 185 ]. A recent study published by Liu et al ( Proc.…”

Circ_0007331 knock‐down suppresses the progression of endometriosis via miR‐200c‐3p/HiF‐1α axis

“…6 Circular RNAs (circRNAs) are a type of regulatory RNAs that lack canonical 5′ cap and 3′ poly-A tail attributed to their covalent closedloop structures. 7 As the competitive endogenous RNAs, circRNAs regulate the expression of multiple genes at the transcriptional and post-transcriptional levels by sponging downstream microRNA (miRNA). Most meaningfully, circRNAs have been increasingly used as the biomarker in the diagnosis, therapy and prognosis of various diseases due to its advantages of abundant expression level, high stability and covalent terminals.…”