Noncoding RNAs in Cardiovascular Disease: Current Knowledge, Tools and Technologies for Investigation, and Future Directions: A Scientific Statement From the American Heart Association
Noncoding RNAs in Cardiovascular Disease: Current Knowledge, Tools and Technologies for Investigation, and Future Directions: A Scientific Statement From the American Heart Association
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DOI：
10.1161/hcg.0000000000000062
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发表时间：
2020-08-01
影响因子：
7.4
通讯作者：
Yin, Ke-Jie
中科院分区：
文献类型：
--
作者：
Das, Saumya;Shah, Ravi;Yin, Ke-Jie
背景资料：大部分非蛋白质编码基因组被转录并在基本细胞过程中发挥多种功能作用的发现，导致了研究这些非编码RNA在心血管健康中作用的工具和技术开发的爆炸式增长。此外，鉴定用于靶向治疗以治疗心血管疾病的非编码RNA是一个新兴的研究领域。本声明的目的是回顾现有的文献，为目前可用于研究非编码RNA的工具和技术提供指导，并确定未满足的需求领域。研究方法：撰写小组使用系统性文献综述（包括MEDLINE，截至2018年的Web of Science），专家意见/声明，数据库和计算工具/算法的分析，以及对当前临床试验的回顾，以提供关于心血管疾病非编码RNA最新技术水平的广泛共识。结果如下：自最初的研究以来，已经取得了重大进展，重点是miRNAs（microRNAs）在心血管发育和疾病中的作用。值得注意的是，最近在理解新型非编码小RNA如snoRNA（小核仁RNA）、tRNA（转移RNA）片段和Y-RNA在细胞过程中的作用方面的进展揭示了许多这些分子的非典型功能。类似地，识别似乎在心血管疾病过程中发挥重要作用的长非编码RNA，再加上开发工具来表征其相互作用的伙伴，导致了显着的机制见解。最后，最近的工作已经表征了细胞外RNA在介导细胞间通讯中的独特作用及其作为生物标志物的潜在作用。结论：用于隔离、测量和注释这些实体的工具和管道的快速扩展表明，在这些方法得到严格验证之前，解释结果时必须谨慎。大多数研究人员都专注于研究单个RNA实体的功能作用，但研究表明不同RNA分子之间存在复杂的相互作用。使用网络方法和先进的计算工具来了解不同的非编码RNA种类的相互作用，以介导特定的表型可能需要充分理解非编码RNA在介导疾病表型的功能。
Background: The discovery that much of the non-protein-coding genome is transcribed and plays a diverse functional role in fundamental cellular processes has led to an explosion in the development of tools and technologies to investigate the role of these noncoding RNAs in cardiovascular health. Furthermore, identifying noncoding RNAs for targeted therapeutics to treat cardiovascular disease is an emerging area of research. The purpose of this statement is to review existing literature, offer guidance on tools and technologies currently available to study noncoding RNAs, and identify areas of unmet need. Methods: The writing group used systematic literature reviews (including MEDLINE, Web of Science through 2018), expert opinion/statements, analyses of databases and computational tools/algorithms, and review of current clinical trials to provide a broad consensus on the current state of the art in noncoding RNA in cardiovascular disease. Results: Significant progress has been made since the initial studies focusing on the role of miRNAs (microRNAs) in cardiovascular development and disease. Notably, recent progress on understanding the role of novel types of noncoding small RNAs such as snoRNAs (small nucleolar RNAs), tRNA (transfer RNA) fragments, and Y-RNAs in cellular processes has revealed a noncanonical function for many of these molecules. Similarly, the identification of long noncoding RNAs that appear to play an important role in cardiovascular disease processes, coupled with the development of tools to characterize their interacting partners, has led to significant mechanistic insight. Finally, recent work has characterized the unique role of extracellular RNAs in mediating intercellular communication and their potential role as biomarkers. Conclusions: The rapid expansion of tools and pipelines for isolating, measuring, and annotating these entities suggests that caution in interpreting results is warranted until these methodologies are rigorously validated. Most investigators have focused on investigating the functional role of single RNA entities, but studies suggest complex interaction between different RNA molecules. The use of network approaches and advanced computational tools to understand the interaction of different noncoding RNA species to mediate a particular phenotype may be required to fully comprehend the function of noncoding RNAs in mediating disease phenotypes.