Genomic analysis of circular RNAs in heart.

Genomic analysis of circular RNAs in heart.
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DOI:
10.1186/s12920-020-00817-7
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发表时间:
2020-11-07
影响因子:
2.7
通讯作者:
Zhou J
Zhou J
中科院分区:
医学3区
文献类型:
--
作者:
Dong K;He X;Su H;Fulton DJR;Zhou J

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心力衰竭是人类发病率和死亡率的主要原因。环状RNA(CircRNA)是近年来发现的一类具有重要生理和病理作用的RNA。在目前的研究中,我们从头分析了来自5个正常和5个扩张型心肌病(DCM)人类心脏样本的现有全转录组数据,并将结果与先前在人类,小鼠和大鼠心脏中报道的circRNA进行了比较。我们的分析确定了一系列在多项研究中可靠检测到的心脏circRNA。我们还定义了健康人类心脏中最丰富的前30种circRNA,其中包括一些以前未被识别的心脏作用,如circHIPK3_11和circTULP4_1。我们进一步发现,许多circRNA在DCM中失调,特别是源自DCM相关基因位点的转录物,如TTN和RYR 2。此外,我们预测了心脏circRNA对已报道在心脏病中发挥作用的miRNAs的海绵作用。我们发现circALMS1_6具有最高的结合miR-133的潜力,miR-133是一种可以调节心脏重塑的microRNA。有趣的是,我们检测到一类新的circRNA,称为read-through(rt)-circRNA,它们由两个不同的相邻基因的外显子产生。具体而言,来自SCAF 8和TIAM 2的rt-circRNA在DCM中被观察到失调,并且这些rt-circRNA具有海绵多个心脏病相关miRNA的潜力。综上所述,本研究为探索circRNA在人类心脏疾病中的功能提供了宝贵的资源,并为在其他组织中识别新的circRNA建立了功能范例。
Heart failure is a leading cause of human morbidity and mortality. Circular RNAs (circRNAs) are a newly discovered class of RNA that have been found to have important physiological and pathological roles. In the current study, we de novo analyzed existing whole transcriptome data from 5 normal and 5 dilated cardiomyopathy (DCM) human heart samples and compared the results with circRNAs that have been previously reported in human, mouse and rat hearts. Our analysis identifies a list of cardiac circRNAs that are reliably detected in multiple studies. We have also defined the top 30 most abundant circRNAs in healthy human hearts which include some with previously unrecognized cardiac roles such as circHIPK3_11 and circTULP4_1. We further found that many circRNAs are dysregulated in DCM, particularly transcripts originating from DCM-related gene loci, such as TTN and RYR2. In addition, we predict the potential of cardiac circRNAs to sponge miRNAs that have reported roles in heart disease. We found that circALMS1_6 has the highest potential to bind miR-133, a microRNA that can regulate cardiac remodeling. Interestingly, we detected a novel class of circRNAs, referred to as read-though (rt)-circRNAs which are produced from exons of two different neighboring genes. Specifically, rt-circRNAs from SCAF8 and TIAM2 were observed to be dysregulated in DCM and these rt-circRNAs have the potential to sponge multiple heart disease-related miRNAs. In summary, this study provides a valuable resource for exploring the function of circRNAs in human heart disease and establishes a functional paradigm for identifying novel circRNAs in other tissues.
DOI: 10.1093/bioinformatics/btu638
发表时间: 2015-01-15
期刊: Bioinformatics (Oxford, England)
影响因子: --
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