Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, 1459 Laney Walker Blvd, Augusta, GA, 30912, USA.
Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
BMC Med Genomics. 2020 Nov 7;13(1):167. doi: 10.1186/s12920-020-00817-7.
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.
心力衰竭是人类发病率和死亡率的主要原因。环状 RNA（circRNAs）是一类新发现的 RNA，已被发现具有重要的生理和病理作用。在本研究中，我们从头分析了 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，并将结果与之前在人类、小鼠和大鼠心脏中报道的 circRNAs 进行了比较。
我们的分析确定了一组在多个研究中可靠检测到的心脏 circRNAs。我们还定义了健康人心脏中最丰富的前 30 个 circRNAs，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 circRNAs 在 DCM 中失调，特别是来自 DCM 相关基因座的转录本，如 TTN 和 RYR2。此外，我们预测了心脏 circRNAs 潜在的海绵状 miRNA，这些 miRNA 在心脏病中有报道作用。我们发现 circALMS1_6 具有结合 miR-133 的最高潜力，miR-133 是一种可以调节心脏重构的 microRNA。有趣的是，我们检测到一类新的 circRNAs，称为读通（rt）-circRNAs，它们是由两个不同相邻基因的外显子产生的。具体来说，观察到 SCAF8 和 TIAM2 的 rt-circRNAs 在 DCM 中失调，这些 rt-circRNAs 具有海绵吸收多种与心脏病相关的 miRNA 的潜力。
总之，本研究为探索 circRNAs 在人类心脏病中的功能提供了有价值的资源，并为在其他组织中识别新的 circRNAs 建立了功能范例。
