Long Noncoding RNAs

Journal of the American College of Cardiology, Journal Year: 2016, Volume and Issue: 67(10), P. 1214 - 1226

Published: March 1, 2016

Language: Английский

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Circular Noncoding RNA HIPK3 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus

Circulation, Journal Year: 2017, Volume and Issue: 136(17), P. 1629 - 1642

Published: Sept. 1, 2017

The vascular complications of diabetes mellitus are the major causes morbidity and mortality among people with diabetes. Circular RNAs a class endogenous noncoding that regulate gene expression in eukaryotes. In this study, we investigated role circular RNA retinal dysfunction induced by mellitus.Quantitative polymerase chain reactions, Sanger sequencing, Northern blots were conducted to detect HIPK3 (circHIPK3) pattern on mellitus-related stresses. MTT (3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assays, EdU (5-ethynyl-2'-deoxyuridine) incorporation Transwell migration Matrigel assays circHIPK3 endothelial cell function vitro. Retinal trypsin digestion, permeability ELISA vivo. Bioinformatics analysis, luciferase activity pull-down vitro studies reveal mechanism circHIPK3-mediated dysfunction.circHIPK3 was significantly upregulated diabetic retinas cells following stressors related mellitus. silencing or overexpressing changed viability, proliferation, migration, tube formation vivo alleviated dysfunction, as shown decreased acellular capillaries, leakage, inflammation. acted an miR-30a-3p sponge sequester inhibit activity, which led increased growth factor-C, FZD4, WNT2 expression. Ectopic mimicked effect phenotypes vitro.The plays retinopathy blocking miR-30a function, leading proliferation dysfunction. These data suggest is potential target control proliferative retinopathy.

Language: Английский

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The long noncoding RNA Malat1: Its physiological and pathophysiological functions

RNA Biology, Journal Year: 2017, Volume and Issue: 14(12), P. 1705 - 1714

Published: Aug. 24, 2017

Recent studies suggest that in humans, DNA sequences responsible for protein coding regions comprise only 2% of the total genome. The rest transcripts result RNA without protein-coding ability, including long noncoding RNAs (lncRNAs). Different from most members lncRNA family, metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is abundantly expressed and evolutionarily conserved throughout various mammalian species. Malat1 one first identified lncRNAs associated with human disease, cumulative have indicated plays critical roles development progression cancers. also actively involved physiologic processes, alternative splicing, epigenetic modification gene expression, synapse formation, myogenesis. Furthermore, extensive evidences show pivotal multiple pathological conditions as well. In this review, we will summarize latest findings related to pathophysiological processes discuss its therapeutic potentials.

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 cardiac development and ageing

Nature Reviews Cardiology, Journal Year: 2015, Volume and Issue: 12(7), P. 415 - 425

Published: April 2, 2015

Language: Английский

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Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

Frontiers in Endocrinology, Journal Year: 2018, Volume and Issue: 9

Published: Jan. 17, 2018

Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead heart failure through variety of mechanisms, including myocardial infarction chronic pressure overload. Pathogenetic mainly linked hyperglycemia sustained hyperinsulinemia, include changes in profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility ischemia, extracellular matrix remodeling. The close relationship between type DM CVD has led the soil hypothesis, postulating that both conditions share genetic environmental factors influencing this association. However, although risk DM, such as obesity, insulin resistance, dyslipidemia, inflammation thrombophilia, can be identified majority affected patients, less known about how these influence conditions, so efforts are still needed for more comprehensive understanding relationship. genetic, epigenetic, backgrounds have been recently studied updated. underlying pathogenetic mechanisms seldom investigated within broader shared background, but rather specific context or CVD, separately. As precise pathophysiological links not entirely understood many aspects require elucidation, an integrated description influences involved concomitant development diseases paramount importance shed new light on interlinks CVD. This review addresses current knowledge overlapping epigenetic microRNAs (miRNAs) long non-coding RNAs (lnc-RNAs), whose abnormal regulation implicated either etiologically cause their progression. Understanding disorders may help drive future research towards approach provide directions field.

Language: Английский

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Long Noncoding RNA Malat1 Regulates Cerebrovascular Pathologies in Ischemic Stroke

Journal of Neuroscience, Journal Year: 2017, Volume and Issue: 37(7), P. 1797 - 1806

Published: Jan. 16, 2017

The study was designed to determine the role of long noncoding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (Malat1), in ischemic stroke outcome. Primary mouse brain microvascular endothelial cells (BMECs) were cultured and treated with Malat1 GapmeR before 16 h oxygen glucose depravation (OGD). Cell death assayed by LDH MTT methods. knock-out wild-type mice subjected middle cerebral artery occlusion (MCAO) 24–72 reperfusion. To explore underlying mechanism, apoptotic inflammatory factors measured qPCR, ELISA, Western blotting. physical interaction between or immunoprecipitation. Increased levels found BMECs after OGD as well isolated microvessels MCAO. Silencing significantly increased OGD-induced cell Caspase 3 activity BMECs. also aggravated expression proapoptotic factor Bim proinflammatory cytokines MCP-1, IL-6, E-selectin. Moreover, KO presented larger infarct size, worsened neurological scores, reduced sensorimotor functions. Consistent vitro findings, cortex compared WT controls. Finally, we demonstrated that binds E-selectin both vivo . Our suggests plays critical protective roles stroke. SIGNIFICANCE STATEMENT Accumulative studies have important regulatory microRNAs vascular neural damage However, functional significance mechanisms other classes RNAs cerebrovascular pathophysiology are less studied. Here demonstrate a novel Malat1, has been originally identified prognostic marker for non-small cancer, pathogenesis experiments provided first evidence anti-apoptotic anti-inflammatory microvasculature reduce parenchymal damages. suggest lncRNAs can be therapeutically targeted minimize poststroke damage.

Language: Английский

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Noncoding RNAs in disease

FEBS Letters, Journal Year: 2018, Volume and Issue: 592(17), P. 2884 - 2900

Published: July 4, 2018

Noncoding RNA s are emerging as potent and multifunctional regulators in all biological processes. In parallel, a rapidly growing number of studies has unravelled associations between aberrant noncoding expression human diseases. These have been extensively reviewed, often with the focus on particular microRNA (mi ) (family) or selected disease/pathology. this Mini‐Review, we highlight selection order to demonstrate wide‐scale involvement mi long pathophysiology three types diseases: cancer, cardiovascular neurological disorders. This research is opening new avenues novel therapeutic approaches.

Language: Английский

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LncRNA as a Therapeutic Target for Angiogenesis

Current Topics in Medicinal Chemistry, Journal Year: 2017, Volume and Issue: 17(15), P. 1750 - 1757

Published: April 26, 2017

Background: Out of 3 billion base pairs in human genome only ~2% code for proteins; and out 180,000 transcripts cells, about 20,000 protein, remaining 160,000 are non-coding transcripts. Most these more than 200 constitute a group long RNA (lncRNA). Many the lncRNA have its own promoter, well conserved mammals. Accumulating evidence indicates that lncRNAs act as molecular switches cellular differentiation, movement, apoptosis, reprogramming cell states by altering gene expression patterns. However, role this important molecules angiogenesis is not understood. Angiogenesis complex process depends on precise regulation expression. Keywords: Epigenetic regulation, expression, intervening noncoding RNA, LncRNA, Linc-MD1.

Language: Английский

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LincRNA-Gm4419 knockdown ameliorates NF-κB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy

Cell Death and Disease, Journal Year: 2017, Volume and Issue: 8(2), P. e2583 - e2583

Published: Feb. 2, 2017

Abstract Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication diabetes. Recent researches have shown activation nuclear factor kappa light-chain enhancer activated B cells (NF- κ B) and NACHT, LRR PYD domain-containing protein 3 (NLRP3) inflammasome are associated with inflammation in progression DN, but exact mechanism unclear. Long noncoding RNAs (lncRNAs) roles development many diseases including DN. However, relationship between lncRNAs DN remains largely unknown. Our previous study has revealed that 14 abnormally expressed by RNA sequencing real-time quantitative PCR (qRT-PCR) renal tissues db/db mice. In this study, these were verified their expressions qRT-PCR mesangial (MCs) cultured under high- low-glucose conditions. Twelve displayed same expressional tendencies both MCs. particular, long intergenic (lincRNA)-Gm4419 was only one associating NF- among 12 bioinformatics methods. Moreover, Gm4419 knockdown could obviously inhibit pro-inflammatory cytokines fibrosis biomarkers, reduce cell proliferation MCs high-glucose condition, whereas overexpression increase inflammation, condition. Interestingly, our results showed activate pathway directly interacting p50, subunit B. addition, we found p50 interact NLRP3 conclusion, findings suggest lincRNA-Gm4419 may participate condition through B/NLRP3 signaling pathway, provide new insights into regulation during

Language: Английский

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