Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, Guangdong, 510080, China.
NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, Guangdong, 510080, China; Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Exp Cell Res. 2022 Sep 1;418(1):113262. doi: 10.1016/j.yexcr.2022.113262. Epub 2022 Jun 14.
Pathological cardiac hypertrophy is an independent risk factor for the development of heart failure. Long noncoding RNAs (lncRNAs), an emerging class of non-protein-coding transcripts, are involved in regulation of multiple cardiac diseases through diverse molecular mechanism, whereas the role of cytoplasmic lncRNAs in regulating cardiac hypertrophy remains unclear. In this study, we identified a novel and functional long noncoding RNA Gm17501, which was predominantly expressed in the cytoplasm of cardiomyocytes. The expression level of lncRNA Gm17501 was altered in cardiac hypertrophy induced by pressure overload and phenylephrine treatment. Moreover, lncRNA Gm17501 expression was decreased in the heart tissue of patients with heart failure. Silencing lncRNA Gm17501 aggravated cardiac hypertrophy under pathological stress. Inhibition of lncRNA Gm17501 did not alter the expression of nearby genes but decreased mRNA level of calcium handling proteins which were involved in cardiac contraction. Therefore, the cytoplasmic lncRNA Gm17501 might protect cardiomyocytes against hypertrophy, possibly by maintaining calcium signaling pathway.
病理性心肌肥厚是心力衰竭发展的独立危险因素。长链非编码 RNA(lncRNA)是一类新兴的非蛋白编码转录本,通过多种分子机制参与多种心脏疾病的调控,而细胞质 lncRNA 在调节心肌肥厚中的作用尚不清楚。在这项研究中,我们鉴定了一种新型的、有功能的长链非编码 RNA Gm17501,它主要在心肌细胞的细胞质中表达。lncRNA Gm17501 的表达水平在压力超负荷和苯肾上腺素处理诱导的心肌肥厚中发生改变。此外,心力衰竭患者的心脏组织中 lncRNA Gm17501 的表达降低。lncRNA Gm17501 沉默在病理性应激下加重心肌肥厚。lncRNA Gm17501 的抑制不改变附近基因的表达,但降低了参与心肌收缩的钙处理蛋白的 mRNA 水平。因此,细胞质 lncRNA Gm17501 可能通过维持钙信号通路来保护心肌细胞免受肥厚。