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长链非编码 RNA 与心脏疾病

Long Noncoding RNAs and Cardiac Disease.

机构信息

1 Molecular Cardiology Laboratory, IRCCS Policlinico San Donato , Milan, Italy .

2 Cardiovascular Research Unit, Luxembourg Institute of Health (LIH) , Luxembourg, Luxembourg .

出版信息

Antioxid Redox Signal. 2018 Sep 20;29(9):880-901. doi: 10.1089/ars.2017.7126. Epub 2017 Aug 30.

DOI:10.1089/ars.2017.7126
PMID:28699361
Abstract

SIGNIFICANCE

To maintain homeostasis, gene expression has to be tightly regulated by complex and multiple mechanisms occurring at the epigenetic, transcriptional, and post-transcriptional levels. One crucial regulatory component is represented by long noncoding RNAs (lncRNAs), nonprotein-coding RNA species implicated in all of these levels. Thus, lncRNAs have been associated with any given process or pathway of interest in a variety of systems, including the heart. Recent Advances: Mounting evidence implicates lncRNAs in cardiovascular diseases (CVD) and progression and their presence in the blood of heart disease patients indicates that they are attractive potential biomarkers.

CRITICAL ISSUES

Our understanding of the regulation and molecular mechanisms of action of most lncRNAs remains rudimentary. A challenge is represented by their often low evolutionary sequence conservation that limits the use of animal models for preclinical studies. Nevertheless, a growing number of lncRNAs with an impact on heart function is rapidly accumulating. In this study, we will discuss (i) lncRNAs that control heart homeostasis and disease; (ii) concepts, approaches, and methodologies necessary to study lncRNAs in the heart; and (iii) challenges posed and opportunities presented by lncRNAs as potential therapeutic targets and biomarkers.

FUTURE DIRECTIONS

A deeper knowledge of the molecular mechanisms underpinning CVDs is necessary to develop more effective treatments. Further studies are needed to clarify the regulation and function of lncRNAs in the heart before they can be considered as therapeutic targets and disease biomarkers. Antioxid. Redox Signal. 29, 880-901.

摘要

意义

为了维持体内平衡,基因表达必须通过发生在表观遗传、转录和转录后水平的复杂和多种机制进行严格调节。一个关键的调节成分是长非编码 RNA(lncRNA),这种非蛋白编码 RNA 物种与所有这些水平都有关联。因此,lncRNA 与包括心脏在内的各种系统中的任何特定过程或途径都有关联。

最新进展

越来越多的证据表明 lncRNA 与心血管疾病(CVD)的发生和进展有关,它们存在于心脏病患者的血液中表明它们是有吸引力的潜在生物标志物。

关键问题

我们对大多数 lncRNA 的调控和分子作用机制的理解仍然很基础。一个挑战是它们的进化序列保守性通常较低,这限制了使用动物模型进行临床前研究。尽管如此,越来越多的对心脏功能有影响的 lncRNA 正在迅速积累。在这项研究中,我们将讨论:(i)控制心脏内稳态和疾病的 lncRNA;(ii)在心脏中研究 lncRNA 所需的概念、方法和方法;以及(iii)作为潜在治疗靶点和生物标志物的 lncRNA 带来的挑战和机遇。

未来方向

为了开发更有效的治疗方法,有必要深入了解 CVD 背后的分子机制。在将 lncRNA 视为治疗靶点和疾病生物标志物之前,还需要进一步研究以阐明它们在心脏中的调控和功能。抗氧化。氧化还原信号。29,880-901。

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