Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches

Physiological Reviews, Journal Year: 2016, Volume and Issue: 96(4), P. 1297 - 1325

Published: Aug. 18, 2016

Advances in RNA-sequencing techniques have led to the discovery of thousands non-coding transcripts with unknown function. There are several types linear RNAs such as microRNAs (miRNA) and long (lncRNA), well circular (circRNA) consisting a closed continuous loop. This review guides reader through important aspects RNA biology. includes their biogenesis, mode actions, physiological function, role disease context (such cancer or cardiovascular system). We specifically focus on potential therapeutic targets diagnostic biomarkers.

Language: Английский

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Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives

European Heart Journal, Journal Year: 2017, Volume and Issue: 39(29), P. 2704 - 2716

Published: March 15, 2017

Recent research has demonstrated that the non-coding genome plays a key role in genetic programming and gene regulation during development as well health cardiovascular disease. About 99% of human do not encode proteins, but are transcriptionally active representing broad spectrum RNAs (ncRNAs) with important regulatory structural functions. Non-coding have been identified critical novel regulators risk factors cell functions thus candidates to improve diagnostics prognosis assessment. Beyond this, ncRNAs rapidly emgerging fundamentally therapeutics. On first level, provide therapeutic targets some which entering assessment clinical trials. second new tools were developed from endogenous serving blueprints. Particularly advanced is RNA interference (RNAi) drugs use recently discovered pathways short interfering becoming versatile for efficient silencing protein expression. Pioneering studies include RNAi targeting liver synthesis PCSK9 resulting highly significant lowering LDL cholesterol or transthyretin (TTR) treatment cardiac TTR amyloidosis. Further mimicking actions may arise exploitation molecular interactions accessible conventional pharmacology. We an update on recent developments perspectives diagnostic diseases, including atherosclerosis/coronary disease, post-myocardial infarction remodelling, heart failure.

Language: Английский

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Long noncoding RNAs in kidney and cardiovascular diseases

Nature Reviews Nephrology, Journal Year: 2016, Volume and Issue: 12(6), P. 360 - 373

Published: May 3, 2016

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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CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis

Journal of Molecular and Cellular Cardiology, Journal Year: 2015, Volume and Issue: 89, P. 98 - 112

Published: Sept. 30, 2015

Long noncoding RNAs (lncRNAs) are emerging as important regulators of developmental pathways. However, their roles in human cardiac precursor cell (CPC) remain unexplored. To characterize the long transcriptome during CPC differentiation, we profiled lncRNA CPCs isolated from fetal heart and identified 570 lncRNAs that were modulated differentiation. Many these associated with active enhancer super enhancers (SE) expression being correlated proximal genes. One most upregulated was a SE-associated named CARMEN, (CAR)diac (M)esoderm (E)nhancer-associated (N)oncoding RNA. CARMEN exhibits RNA-dependent enhancing activity is upstream mesoderm-specifying gene regulatory network. Interestingly, interacts SUZ12 EZH2, two components polycomb repressive complex 2 (PRC2). We demonstrate knockdown inhibits specification differentiation cells independently MIR-143 -145 expression, microRNAs located to sequences. Importantly, activated pathological remodeling mouse hearts, necessary for maintaining identity differentiated cardiomyocytes. This study demonstrates therefore crucial regulator homeostasis.

Language: Английский

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Epigenetic Modifications in Cardiovascular Aging and Diseases

Circulation Research, Journal Year: 2018, Volume and Issue: 123(7), P. 773 - 786

Published: Sept. 13, 2018

Aging is associated with a progressive decline in cardiovascular structure and function. Accumulating evidence links aging to epigenetic alterations encompassing complex interplay of DNA methylation, histone posttranslational modifications, dynamic nucleosome occupancy governed by numerous factors. Advances genomics technology have led profound understanding chromatin reorganization both diseases. This review summarizes recent discoveries mechanisms involved diseases discusses potential therapeutic strategies retard conquer related through the rejuvenation signatures young state.

Language: Английский

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Long Noncoding RNAs in Cardiovascular Pathology, Diagnosis, and Therapy

Circulation, Journal Year: 2016, Volume and Issue: 134(19), P. 1484 - 1499

Published: Nov. 7, 2016

Vast parts of mammalian genomes encode for transcripts that are not further translated into proteins. The purpose the majority such noncoding ribonucleic acids (RNAs) remained paradoxical a long time. However, growing body evidence demonstrates RNAs dynamically expressed in different cell types, diseases, or developmental stages to execute wide variety regulatory roles at virtually every step gene expression and translation. Indeed, influence via epigenetic modulations, through regulating alternative splicing, by acting as molecular sponges. abundance cardiovascular system indicates they may be part complex network governing physiology pathology heart. In this review, we discuss multifaceted functions highlight current literature with an emphasis on cardiac development disease. Furthermore, enormous spectrum potentially opens up new avenues diagnosis prevention heart failure, ultimately evaluate futuristic prospects biomarkers, therapeutic targets treatment disorders, well.

Language: Английский

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Long non-coding RNA and chromatin remodeling

RNA Biology, Journal Year: 2015, Volume and Issue: 12(10), P. 1094 - 1098

Published: July 15, 2015

Long noncoding RNAs (lncRNAs) are pivotal regulators of genome structure and gene expression. LncRNAs can directly interact with chromatin-modifying enzymes nucleosome-remodeling factors to control chromatin accessibility genetic information. Moreover, lncRNA expression be controlled by chromatin-remodeling factors, suggesting a feedback circuit regulation. Here, we discuss the recent advances studies, focusing on function mechanism lncRNA-chromatin interactions.

Language: Английский

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Crosstalk between Long Noncoding RNAs and MicroRNAs in Health and Disease

International Journal of Molecular Sciences, Journal Year: 2016, Volume and Issue: 17(3), P. 356 - 356

Published: March 11, 2016

Protein-coding genes account for only a small part of the human genome; in fact, vast majority transcripts are comprised non-coding RNAs (ncRNAs) including long ncRNAs (lncRNAs) and ncRNAs, microRNAs (miRs). Accumulating evidence indicates that could play critical roles regulating many cellular processes which often implicated health disease. For example, aberrantly expressed cancers, heart diseases, other diseases. LncRNAs miRs therefore novel promising targets to be developed into biomarkers diagnosis prognosis as well treatment options. The interaction between lncRNAs its pathophysiological significance have recently been reported. Mechanistically, it is believed exert “sponge-like” effects on various miRs, subsequently inhibits miR-mediated functions. This crosstalk two types frequently contributes pathogenesis In this review, we provide summary recent studies highlighting these disease regulation.

Language: Английский

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Long non-coding RNAs as novel targets for therapy in hepatocellular carcinoma

Pharmacology & Therapeutics, Journal Year: 2016, Volume and Issue: 161, P. 67 - 78

Published: March 22, 2016

The recognition of functional roles for transcribed long non-coding RNA (lncRNA) has provided a new dimension to our understanding cellular physiology and disease pathogenesis. LncRNAs are large group structurally complex genes that can interact with DNA, RNA, or protein molecules modulate gene expression exert effects through diverse mechanisms. emerging knowledge regarding their aberrant in states emphasizes the potential lncRNA serve as targets therapeutic intervention. In this concise review, we outline mechanisms action lncRNAs, roles, involvement disease. Using liver cancer an example, provide overview opportunities approaches target lncRNA-dependent purposes.

Language: Английский

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