Circular RNA and its mechanisms in disease: From the bench to the clinic

Pharmacology & Therapeutics, Journal Year: 2018, Volume and Issue: 187, P. 31 - 44

Published: Feb. 14, 2018

Language: Английский

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Circular RNAs: Biogenesis, Function and Role in Human Diseases

Frontiers in Molecular Biosciences, Journal Year: 2017, Volume and Issue: 4

Published: June 5, 2017

Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act gene regulators in mammals. They were originally thought to represent errors splicing considered be of low abundance, however, there is now an increased appreciation their important function regulation. circRNAs differentially generated by backsplicing exons or from lariat introns. Unlike RNA, the 3′ 5′ ends normally present molecule have been joined together covalent bonds leading circularisation. Interestingly, they found abundant, evolutionally conserved relatively stable cytoplasm. These features confer numerous potential functions circRNAs, such acting miRNA sponges, binding RNA-associated proteins RNA-protein complexes that regulate transcription. It has proposed circRNA expression at transcriptional post-transcriptional level interacting with miRNAs may a role regulating cancer initiation progression. appear more often downregulated tumour tissue compared normal this due (i) back-splice machinery malignant tissues, (ii) degradation deregulated (iii) increasing cell proliferation reduction circRNAs. identified exosomes recently, chromosomal translocations shown generate aberrant fusion-circRNAs associated resistance drug treatments. In addition, though non-coding, evidence suggest select can translated into functional proteins. Although much remains elucidated about biology mechanisms regulation, these ncRNAs quickly emerging disease biomarkers therapeutic targets cancer.

Language: Английский

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Circular RNA in cardiovascular disease

Journal of Cellular Physiology, Journal Year: 2018, Volume and Issue: 234(5), P. 5588 - 5600

Published: Oct. 20, 2018

Abstract Circular RNA (circRNA) are endogenous transcripts that display differential expression across species, developmental stages, and pathologies. Their lack of free ends confers increased stability when compared with linear transcripts, making them ideal candidates for future diagnostic biomarkers therapeutic interventions. Increasing evidence has implicated circRNA in the pathogenesis multiple cardiovascular diseases. In this paper, we summarize current understanding biogenesis, properties, profiles, detection methods, functions, their implication cardiac pathologies including/ischemia reperfusion injury, myocardial infarction, senescence, fibrosis, cardiomyopathy, hypertrophy heart failure, atherosclerosis, coronary artery disease, aneurysm.

Language: Английский

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Targeting circular RNAs as a therapeutic approach: current strategies and challenges

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: May 21, 2021

Abstract Significant progress has been made in circular RNA (circRNA) research recent years. Increasing evidence suggests that circRNAs play important roles many cellular processes, and their dysregulation is implicated the pathogenesis of various diseases. CircRNAs are highly stable usually expressed a tissue- or cell type-specific manner. Therefore, they currently being explored as potential therapeutic targets. Gain-of-function loss-of-function approaches typically performed using circRNA expression plasmids interference-based strategies, respectively. These strategies have limitations can be mitigated nanoparticle exosome delivery systems. Furthermore, developments show cre-lox system used to knockdown cell-specific While still early stages development, CRISPR/Cas13 shown promise knocking down with high specificity efficiency. In this review, we describe properties functions highlight significance disease. We summarize overexpress approach. Lastly, discuss major challenges propose future directions for development circRNA-based therapeutics.

Language: Английский

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CircRNAs and cancer: Biomarkers and master regulators

Seminars in Cancer Biology, Journal Year: 2018, Volume and Issue: 58, P. 90 - 99

Published: Dec. 11, 2018

Language: Английский

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Circular RNAs open a new chapter in cardiovascular biology

Nature Reviews Cardiology, Journal Year: 2019, Volume and Issue: 16(8), P. 503 - 514

Published: April 5, 2019

Language: Английский

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Molecular roles and function of circular RNAs in eukaryotic cells

Cellular and Molecular Life Sciences, Journal Year: 2017, Volume and Issue: 75(6), P. 1071 - 1098

Published: Nov. 7, 2017

Protein-coding and noncoding genes in eukaryotes are typically expressed as linear messenger RNAs, with exons arranged colinearly to their genomic order. Recent advances sequencing mapping RNA reads reference genomes have revealed that thousands of express also covalently closed circular RNAs. Many these circRNAs stable contain exons, but not translated into proteins. Here, we review the emerging understanding both, produced by co- posttranscriptional head-to-tail "backsplicing" a downstream splice donor more upstream acceptor, well generated from intronic lariats during colinear splicing, may exhibit physiologically relevant regulatory functions eukaryotes. We describe how impact gene expression host locus affecting transcriptional initiation elongation or they partake controlling function other molecules, for example interacting microRNAs conclude an outlook circRNA dysregulation affects disease, stability might be exploited biomedical applications.

Language: Английский

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CircRNAs: role in human diseases and potential use as biomarkers

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(5)

Published: May 11, 2021

Circular RNAs (circRNAs) are a class of endogenous characterized by covalent loop structure. In comparison to other types RNAs, the abundance circRNAs is relatively low but due circular configuration, their stability very high. addition, display high degree tissue specificity. The sponging activity toward microRNAs best-described mode action circRNAs. However, ability bind with specific proteins, as well encode short propose alternative functions. This review introduces biogenesis and summarizes roles played in human diseases. These include examples functional several organ-specific cancers, such head neck breast lung cancers. we potential functions diabetes, cardiovascular, neurodegenerative Recently, growing number studies have demonstrated involvement wide spectrum signaling molecular pathways, at same time many different controversial views on role function emerging. We conclude offering cellular homeostasis generated networks comprising non-coding RNA-binding proteins. Accordingly, it predictable that circRNAs, highly stable nature remarkable specificity, will emerge reliable biomarkers disease course treatment efficacy.

Language: Английский

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RNA-based diagnostic and therapeutic strategies for cardiovascular disease

Nature Reviews Cardiology, Journal Year: 2019, Volume and Issue: 16(11), P. 661 - 674

Published: June 11, 2019

Language: Английский

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Specific expression and functions of circular RNAs

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(3), P. 481 - 491

Published: Feb. 15, 2022

Language: Английский

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