Transcriptome Analysis of Canine Cardiac Fat Pads: Involvement of Two Novel Long Non-Coding RNAs in Atrial Fibrillation Neural Remodeling.
Transcriptome Analysis of Canine Cardiac Fat Pads: Involvement of Two Novel Long Non-Coding RNAs in Atrial Fibrillation Neural Remodeling.
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犬心脏脂肪垫的转录组分析：两种新型长非编码 RNA 参与心房颤动神经重塑。
DOI：
10.1002/jcb.25037
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发表时间：
2015
影响因子：
4
通讯作者：
Hou Yinglong
中科院分区：
文献类型：
--
作者：
Wang Weizong;Wang Ximin;Zhang Yujiao;Li Zhan;Xie Xinxing;Wang Jiangrong;Gao Mei;Zhang Shuyu;Hou Yinglong
据报道，内在心脏自主神经重构（ANR）参与心房颤动（AF）的发生和维持。长链非编码rna （lncRNAs）是基因调控网络的重要协调者。然而，我们对房颤中lncRNAs与心脏ANR之间的关系知之甚少。在这项研究中，我们使用第二代RNA测序来检测房颤和非房颤犬心脏脂肪垫中lncRNAs的转录组。总共获得了61,616个推测的lncrna，其中166个下调，410个上调，变化幅度超过两倍。生物信息学分析表明，异常表达的基因与神经发育、迁移和神经退行性疾病有关。在一系列滤波管道的基础上，选择了两个新的lncrna，即tcon_00032546和tcon_00026102。慢病毒在体内沉默tcon_00032546或tcon_00026102可显著缩短或延长心房有效不应期，从而通过促进或抑制神经发生增加或阻止心房颤动的诱导。此外，CCND1‐FGF19‐FGF4‐FGF3基因簇和tcon_00032546和tcon_00026102的邻近基因SLC25A4的表达与lncrna的表达呈负相关。此外，结合生物信息学分析和文献综述，tcon_00032546和tcon_00026102可能在神经重构过程中通过复杂的机制增加CCND1‐FGF19‐FGF3‐FGF4基因群和SLC25A4，从而诱导作用。综上所述，失调的lncrna可能在房颤神经重塑中发挥调节作用，这可能进一步为房颤的预防和治疗提供潜在的治疗靶点。中国生物医学工程学报，2016,31(2):389 - 391。©2015 Wiley期刊公司
Intrinsic cardiac autonomic neural remodeling (ANR) has been reported to be involved in the initiation and maintenance of atrial fibrillation (AF). Long non‐coding RNAs (lncRNAs) are important orchestrators of gene regulatory networks. However, little is known about the relationships between lncRNAs and cardiac ANR in AF. In this study, second‐generation RNA sequencing was performed to examine the transcriptomes of lncRNAs in AF and non‐AF canine cardiac fat pads. A total of 61,616 putative lncRNAs were yielded, in which 166 were downregulated and 410 were upregulated with more than twofold change. Bioinformatics analysis showed that the aberrantly expressed genes were associated with neural development, migration and neurodegenerative disorders. On the basis of a series of filtering pipelines, two new lncRNAs, namely, TCONS_00032546 and TCONS_00026102, were selected. Silencing of TCONS_00032546 or TCONS_00026102 with lentiviruses in vivo could significantly shorten or prolong the atrial effective refractory period thereby increasing or preventing AF inducibility by promoting or inhibiting the neurogenesis. Besides, the expression of CCND1‐FGF19‐FGF4‐FGF3 gene cluster and SLC25A4, the nearby genes of TCONS_00032546 and TCONS_00026102, were negatively correlated with that of lncRNAs. Furthermore, combining bioinformatics analysis with literature review, TCONS_00032546 and TCONS_00026102 may induce effects by increasing the CCND1‐FGF19‐FGF3‐FGF4 gene cluster and SLC25A4 via complex mechanisms during neural remodeling. Taken together, dysregulated lncRNAs may play regulatory roles in AF neural remodeling, which may further provide potential therapeutic targets for prophylaxis and treatment of AF. J. Cell. Biochem. 116: 809–821, 2015. © 2015 Wiley Periodicals, Inc.