Circular RNA in disease: Basic properties and biomedical relevance

Abstract

Circular RNAs (circRNAs) represent a class of covalently closed RNA molecules with great diversity in molecular features, functions, and regulatory mechanisms. Emerging advances in our understanding of circRNA biogenesis, nuclear export, and stability control have been made very recently. In particular, novel roles of circRNAs in diverse human diseases are increasingly recognized. Various circRNAs have been found to affect many disease-relevant pathways through a diverse array of mechanisms, including forming R-loops, sponging miRNAs or proteins, and translating functional proteins, resulting in different pathological phenotypes. This recent progress calls for a revised view of circRNAs in diseases threatening the lives and health of humans. In this review, we focus on the recently described functional relevance of diseaseassociated circRNAs as well as the potential of circRNAs in diverse clinical applications. This article is categorized under: RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs K E Y W O R D S circular RNA, clinical application, nonimmunological disease 1 | INTRODUCTION Circular RNAs (circRNAs) are noncanonical splicing products with covalently closed loop structures. Comprehensive studies of circRNAs have transformed the view of circRNAs from accidental by-products of mis-splicing to stable and evolutionarily conserved molecules, which are specifically expressed in various cells, tissues, or developmental stages of eukaryotes, prokaryotes, and viruses (

Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

“…The latest achievements in molecular biology allow us to assess the role of exosomal circRNAs in cancer resistance to cisplatin treatment. This form of nucleic acid is primarily responsible for controlling parental gene expression through various mechanisms, including miR sponges [ 85 ], which is particularly important in understanding the role of exosomal circRNAs in cancer cells acquiring cisplatin resistance. As with lncRNA, circRNA disrupts the miR-mRNA axis by decreasing miR and consequently increasing the mRNA expression of several oncogenes, leading to the acquisition of resistance to cisplatin.…”

Noncoding RNA therapeutics for substance use disorder

“…Approximately 20% of mammalian genes express circRNAs, and while these ncRNAs are present in various organs, their enriched expression in the brain makes them an appealing target for the treatment of neuropsychiatric disorders ( 117 , 118 ). circRNAs play important roles as transcriptional, post-transcriptional, and/or translational regulators through various mechanisms, most notably as a sponge for miRs ( 119 ). Compared to linear RNAs, circRNAs are highly stable ( 120 ), and thus may also mediate long-term effects in several disease states.…”

circNFXL1 Modulates the Kv2.1 Channel Function in Hypoxic Human Pulmonary Artery Smooth Muscle Cells via Sponging miR-29b-2-5p as a Competitive Endogenous RNA

“…9 With covalently closed structures, circRNAs express specifically and stably in eukaryotes, acting as miRNA sponges, transcriptional factors, translational templates, binding RNAs, or scaffolding of proteins to affect cell behavior. [10][11][12] Recent studies have indicated that circRNAs express abnormally in PAH patients and animal models, contributing to the development and progression of PAH. 13 It has been found that certain cirRNAs, 14 including hsa_-circ_0002062, hsa_circ_0022342, hsa_circ_0016070, and circ-calm4 dysregulated in PAH patients or/and experimental PAH models, show proproliferation effects on PASMCs and association with the vascular remodeling in PAH.…”