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长链非编码 RNA 在肥厚型心肌病中的作用研究:描述性综述。

Reconnoitering the Role of Long-Noncoding RNAs in Hypertrophic Cardiomyopathy: A Descriptive Review.

机构信息

Department of Basic Medical Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab Emirates.

Dubai Health Authority, Dubai 66566, United Arab Emirates.

出版信息

Int J Mol Sci. 2021 Aug 29;22(17):9378. doi: 10.3390/ijms22179378.

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common form of hereditary cardiomyopathy. It is characterized by an unexplained non-dilated hypertrophy of the left ventricle with a conserved or elevated ejection fraction. It is a genetically heterogeneous disease largely caused by variants of genes encoding for cardiac sarcomere proteins, including , , , , , , , and . Preclinical evidence indicates that the enhanced calcium sensitivity of the myofilaments plays a key role in the pathophysiology of HCM. Notably, this is not always a direct consequence of sarcomeric variations but may also result from secondary mutation-driven alterations. Long non-coding RNAs (lncRNAs) are a large class of transcripts ≥200 nucleotides in length that do not encode proteins. Compared to coding mRNAs, most lncRNAs are not as well-annotated and their functions are greatly unexplored. Nevertheless, increasing evidence shows that lncRNAs are involved in a variety of biological processes and diseases including HCM. Accumulating evidence has indicated that lncRNAs are dysregulated in HCM, and closely related to sarcomere construction, calcium channeling and homeostasis of mitochondria. In this review, we have summarized the known regulatory and functional roles of lncRNAs in HCM.

摘要

肥厚型心肌病(HCM)是最常见的遗传性心肌病。其特征为左心室不明原因的非扩张性肥厚,射血分数正常或升高。这是一种遗传异质性疾病,主要由编码心肌肌节蛋白的基因突变引起,包括、、、、、、和。临床前证据表明,肌球蛋白丝的钙敏感性增强在 HCM 的病理生理学中起关键作用。值得注意的是,这并不总是肌节变异的直接后果,也可能是由继发突变驱动的改变引起的。长链非编码 RNA(lncRNA)是一类长度≥200 个核苷酸的转录本,不编码蛋白质。与编码的 mRNA 相比,大多数 lncRNA 注释较差,其功能也未得到充分探索。然而,越来越多的证据表明,lncRNA 参与了多种生物学过程和疾病,包括 HCM。越来越多的证据表明,lncRNA 在 HCM 中失调,与肌节构建、钙通道和线粒体稳态密切相关。在这篇综述中,我们总结了已知的 lncRNA 在 HCM 中的调节和功能作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/445f/8430576/702a0e879ebf/ijms-22-09378-g001.jpg

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