Novel heart specific long non-coding RNAs contribute to pathogenesis of Arrhythmogenic Cardiomyopathy [ARVC patients' heart LV]

Arrhythmogenic cardiomyopathy (AC) is an inherited cardiomyopathy characterized by fibrofatty replacement predominantly involved in right ventricle and clinically by ventricular arrhythmias.In this study, we set out to characterize the cardiac novel long-noncoding RNAs using deep RNA sequencing data from human heart tissues. Particularly, we identified AC specific novel lncRNAs that contribute to AC pathophysiology by comparing the lncRNAs transcripts of nine AC explanted hearts (RV), five non-diseased donor hearts (RV), four non-AC failing hearts (dilated cardiomyopathy, RV). To dissect the roles of novel lncRNAs in ARVC from LV, we also include six non-diseased donor hearts (LV; GSE107125) and six ARVC explanted hearts (LV) in the analysis. In the identified novel AC lncRNAs, a large part of them are derived from enhancer regions and acting as cis- elements to potentially regulate lipogenesis or lipid metabolism related genes. Finally, we validated several of these AC specific novel lncRNAs and their potential targets in independent patient samples. Collectively, we identified high-confidence AC specific novel lncRNAs from human samples and suggest their potential roles as cis- elements in AC pathology. Further study of these novel AC lncRNAs could provide new opportunities for diagnosis and therapeutic intervention. Please note that the GSE107157 records represent the 'five non-diseased donor hearts (RV) and six non-diseased donor hearts (LV)' data. Overall design: RNAseq for ARVC patients' heart LV

致心律失常性心肌病（Arrhythmogenic cardiomyopathy, AC）是一种遗传性心肌病，以纤维脂肪组织替代为主要病理特征，病变主要累及右心室，临床表现为室性心律失常。本研究旨在利用人类心脏组织的深度RNA测序数据，对心脏新型长链非编码RNA（long non-coding RNA, lncRNA）开展特征解析。具体而言，本研究通过比对9例AC患者切除的右心室（right ventricle, RV）心脏组织、5例无病变供体右心室心脏组织、4例非AC衰竭心脏（扩张型心肌病，RV）的lncRNA转录本，筛选出了参与AC病理生理过程的AC特异性新型lncRNA。为解析左心室（left ventricle, LV）来源的新型lncRNA在致心律失常性右心室心肌病（Arrhythmogenic Right Ventricular Cardiomyopathy, ARVC）中的作用，本研究同时纳入了6例无病变供体左心室心脏组织（GSE107125）以及6例ARVC患者切除的左心室心脏组织用于分析。在筛选得到的AC特异性新型lncRNA中，大部分源自增强子区域，并作为顺式作用元件潜在调控脂生成或脂质代谢相关基因。最后，本研究在独立的患者样本中验证了部分此类AC特异性新型lncRNA及其潜在靶基因。综上，本研究从人类样本中筛选得到了高可信度的AC特异性新型lncRNA，并提示其作为顺式作用元件在AC的病理发生过程中发挥潜在作用。对这些新型AC lncRNA的进一步研究，可为疾病的诊断与治疗干预提供新的思路。请注意，GSE107157数据集记录对应的是"5例无病变供体右心室心脏组织与6例无病变供体左心室心脏组织"的测序数据。整体实验设计：ARVC患者左心室心脏组织的RNA测序