Su Ying, Li Long, Zhao Sheng, Yue Yunan, Yang Shuixiang
Department of Cardiology, Beijing Shijitan Hospital Affiliated Capital Medical University, Beijing, China.
Department of Cardiology, Beijing Shijitan Hospital Affiliated Capital Medical University, Beijing, China; Department of Cardiology, Hebei Medical University Affiliated Yiling Hospital, Hebei, China.
Gene. 2018 Feb 5;642:125-134. doi: 10.1016/j.gene.2017.11.025. Epub 2017 Nov 10.
Long noncoding RNAs (lncRNAs) represent a novel class of noncoding RNAs that are involved in a variety of biological processes and human diseases. Recent evidence suggested that lncRNAs were associated with cardiac disorders. However, the roles of lncRNAs in paroxysmal atrial fibrillation (PAF) remain elusive. The purpose of the present study was to identify differentially expressed lncRNAs in PAF and predict their potential functions.
Between May 2014 and December 2015, a total of 67 patients, including 34 patients with PAF and 33 patients without PAF were recruited in this study. Of these participants, 3 PAF patients and 3 controls were used for the microarray analysis and a separate cohort (31 PAF patients and 30 controls) were used for further validation. LncRNA profiles in the leukocytes were detected by microarray.
A total of 2095 and 1584 differentially expressed lncRNAs and mRNAs, respectively, were identified between the PAF patients and controls. Four lncRNAs (uc002nvy.3, ENST00000561094, uc004aef.3, ENST00000559960) were randomly selected for quantitative real-time PCR (qRT-PCR) in a separate cohort, validating that ENST00000559960 was upregulated and uc004aef.3 was downregulated in the PAF patients. uc002nvy.3 and ENST00000561094 showed no significant difference between PAF and the controls. Multiple logistic analyses showed that ENST00000559960 (OR 1.47; 95% CI 1.09 to 2.00; P=0.01) and uc004aef.3 (OR 0.63; 95% CI 0.41 to 0.96; P=0.03) were independently associated with PAF. Receiver operating characteristic (ROC) curves analyses revealed that ENST00000559960 and uc004aef.3 were modest predictors of PAF. The area under the curve (AUC) was 0.67±0.07 (95% CI 0.54-0.81; P=0.02) for uc004aef.3 and 0.70±0.07 (95% CI 0.56-0.83; P<0.01) for ENST00000559960. Bioinformatic analyses (lncRNAs classification and subgroup, gene ontology analysis, pathway analysis and gene co-expression network construction) were performed for predicting the role of lncRNAs.
Our results demonstrated that lncRNA profiles were differentially expressed in the PAF leukocytes, and two lncRNAs (ENST00000559960 and uc004aef.3) may help in prediction of PAF. This motivates further investigation of the role of lncRNAs for PAF.
长链非编码RNA（lncRNAs）是一类新型的非编码RNA，参与多种生物学过程和人类疾病。最近的证据表明lncRNAs与心脏疾病有关。然而，lncRNAs在阵发性心房颤动（PAF）中的作用仍不清楚。本研究的目的是鉴定PAF中差异表达的lncRNAs并预测其潜在功能。
在2014年5月至2015年12月期间，本研究共招募了67例患者，包括34例PAF患者和33例非PAF患者。在这些参与者中，3例PAF患者和3例对照用于微阵列分析，另一个队列（31例PAF患者和30例对照）用于进一步验证。通过微阵列检测白细胞中的lncRNA谱。
在PAF患者和对照之间分别鉴定出总共2095个和1584个差异表达的lncRNAs和mRNAs。在另一个队列中随机选择4个lncRNAs（uc002nvy.3、ENST00000561094、uc004aef.3、ENST00000559960）进行定量实时PCR（qRT-PCR），验证了PAF患者中ENST00000559960上调而uc004aef.3下调。uc002nvy.3和ENST00000561094在PAF和对照之间无显著差异。多因素逻辑分析显示ENST00000559960（OR 1.47；95%CI 1.09至2.00；P=0.01）和uc004aef.3（OR 0.63；95%CI 0.41至0.96；P=0.03）与PAF独立相关。受试者工作特征（ROC）曲线分析显示ENST00000559960和uc004aef.3是PAF的中等预测指标。uc004aef.3的曲线下面积（AUC）为0.67±0.07（95%CI 0.54 - 0.81；P=0.02），ENST00000559960的AUC为0.70±0.07（95%CI 0.56 - 0.83；P<0.01）。进行了生物信息学分析（lncRNAs分类和亚组、基因本体分析、通路分析和基因共表达网络构建）以预测lncRNAs的作用。
我们的结果表明lncRNA谱在PAF白细胞中差异表达，并且两个lncRNAs（ENST00000559960和uc004aef.3）可能有助于PAF的预测。这促使进一步研究lncRNAs在PAF中的作用。
