缺血性和非缺血性扩张型心肌病所致心力衰竭患者长链非编码RNA的独特循环表达谱
Distinct Circulating Expression Profiles of Long Noncoding RNAs in Heart Failure Patients With Ischemic and Nonischemic Dilated Cardiomyopathy.
作者信息
Lin Fang, Gong Xin, Yu Ping, Yue Aixue, Meng Qingshu, Zheng Liang, Chen Tian, Han Lu, Cao Hao, Cao Jianhong, Liang Xiaoting, Hu Hao, Li Yuan, Liu Zhongmin, Zhou Xiaohui, Fan Huimin
机构信息
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
出版信息
Front Genet. 2019 Nov 12;10:1116. doi: 10.3389/fgene.2019.01116. eCollection 2019.
Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), with distinct long-term prognosis and responses to treatment, are two major problems that lead to heart failure (HF) ultimately. In this study, we investigated the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expressions in the plasma of patients with DCM and ICM and analyzed the different lncRNA profile between the two groups. The microarray analysis identified 3,222 and 1,911 significantly differentially expressed lncRNAs and mRNAs between DCM and ICM group. The most enriched upregulated functional terms included positive regulation of I-kappaB kinase/nuclear factor-kappaB signaling and regulation of cellular localization, while the top 10 downregulated genes mainly consisted of acid secretion and myosin heavy chain binding. Furthermore, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed lncRNA-coexpressed mRNAs between DCM and ICM group were significantly enriched in the natural killer cell mediated cytotoxicity and ras signaling pathway respectively. Quantitative real-time PCR confirmed 8 of 12 lncRNAs were upregulated in DCM group compared to ICM group which was consistent with the initial microarray results. The lncRNA/mRNA coexpression network indicated the possible functions of the validated lncRNAs. These findings revealed for the first time the specific expression pattern of both protein-coding RNAs and lncRNAs in plasma of HF patients due to DCM and ICM which may provide some important evidence to conveniently identify the etiology of myocardial dysfunctions and help to explore a better strategy for future HF prognosis evaluation.
缺血性心肌病(ICM)和扩张型心肌病(DCM)是导致心力衰竭(HF)的两个主要问题,它们具有不同的长期预后和对治疗的反应。在本研究中,我们调查了DCM和ICM患者血浆中的长链非编码RNA(lncRNA)和信使RNA(mRNA)表达,并分析了两组之间不同的lncRNA谱。微阵列分析确定了DCM组和ICM组之间分别有3222个和1911个显著差异表达的lncRNA和mRNA。最富集的上调功能术语包括I-κB激酶/核因子-κB信号的正调控和细胞定位调控,而前10个下调基因主要包括酸分泌和肌球蛋白重链结合。此外,京都基因与基因组百科全书通路分析显示,DCM组和ICM组之间差异表达的lncRNA共表达的mRNA分别在自然杀伤细胞介导的细胞毒性和ras信号通路中显著富集。定量实时PCR证实,与ICM组相比,DCM组12个lncRNA中有8个上调,这与最初的微阵列结果一致。lncRNA/mRNA共表达网络表明了验证的lncRNA的可能功能。这些发现首次揭示了DCM和ICM所致HF患者血浆中蛋白质编码RNA和lncRNA的特异性表达模式,这可能为方便地识别心肌功能障碍的病因提供一些重要证据,并有助于探索未来HF预后评估的更好策略。
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