Identification of a long noncoding RNA Gm17501 as a novel negative regulator of cardiac hypertrophy.
Identification of a long noncoding RNA Gm17501 as a novel negative regulator of cardiac hypertrophy.
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DOI：
10.1016/j.yexcr.2022.113262
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发表时间：
2022-06
影响因子：
3.7
通讯作者：
Zhuomin Liang;Wendong Fan;Hao Chen;Zhan-Peng Huang;R. Fang;Bin Dong;Chen Chen-Chen;Jiayong Li;
中科院分区：
文献类型：
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作者：
Zhuomin Liang;Wendong Fan;Hao Chen;Zhan-Peng Huang;R. Fang;Bin Dong;Chen Chen-Chen;Jiayong Li;
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（longnoncodingRNA，lncRNA）是一类新出现的非蛋白质编码转录物，通过多种分子机制参与多种心脏疾病的调控，而胞浆lncRNA在心肌肥厚中的作用尚不清楚。在这项研究中，我们确定了一个新的和功能性的长非编码RNA Gm17501，这主要是在心肌细胞的细胞质中表达。在压力超负荷和苯异丙基肾上腺素诱导的心肌肥厚中，lncRNA Gm17501的表达水平发生了变化。此外，lncRNA Gm17501在心力衰竭患者的心脏组织中的表达降低。在病理性应激下，lncRNA Gm17501沉默加重心肌肥厚。抑制lncRNA Gm17501并不改变附近基因的表达，但降低参与心脏收缩的钙处理蛋白的mRNA水平。因此，胞浆lncRNA Gm17501可能通过维持钙信号通路来保护心肌细胞免受肥大。
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.