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基于 RNA 测序的心房颤动中功能性长非编码 RNA 的鉴定。

Identification of functional lncRNAs in atrial fibrillation based on RNA sequencing.

机构信息

Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.

Department of Cardiology, Bengbu First People's Hospital, Bengbu, Anhui, 233000, China.

出版信息

BMC Cardiovasc Disord. 2023 Nov 6;23(1):539. doi: 10.1186/s12872-023-03573-5.

DOI:10.1186/s12872-023-03573-5
PMID:37932671
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10626701/
Abstract

BACKGROUND

Atrial fibrillation (AF) is one of the most common arrhythmia contributing to serious conditions such as stroke and heart failure. Recent studies demonstrated that long noncoding RNAs (lncRNAs) were related to cardiovascular disease. However, the molecular mechanisms of AF are not fully clear. This study intended to discover lncRNAs that are differentially expressed in AF compared with controls and evaluate the potential functions of these lncRNAs.

METHODS

Ninety-seven patients (49 patients with AF and 48 patients without AF) were included in this study. Among these patients, leucocyte suspensions of 3 AF patients and 3 controls were sent for RNA-seq analysis to select differentially expressed lncRNA and mRNA. Different lncRNA expressions were validated in another samples (46 AF patients and 45 controls). Gene ontology (GO) enrichment analysis was conducted to annotate the function of selected mRNAs. Alternative splicing (AS) analysis was performed and a lncRNA-mRNA network was also constructed. The receiver operating characteristics (ROC) curve was used to evaluate diagnostic values. Logistic regression analysis was utilized to assess the risk or protective factor of AF.

RESULTS

A total of 223 mRNAs and 105 lncRNAs were detected in AF patients compared with controls. Total 4 lncRNAs (LINC01781, AC009509.2, AL662844.3, AL662844.4) associated with AF were picked out for validation in another samples by quantitative real-time PCR (qRT-PCR), detecting that upregulated AC009509.2 and downregulated LINC01781 in AF patients. Multivariate logistic regression analysis illustrated that left atrial diameter (OR 1.201; 95% CI 1.093-1.320; P=0.000) and AC009509.2 (OR 1.732; 95% CI 1.092-2.747; P=0.020) were related to AF respectively. ROC curve showed that AC009509.2, LINC01781 and left atrial diameter (LAD) were predictors of AF. For LINC01781, the area under the curve (AUC) was 0.654 (95% CI 0.541-0.767, P=0.0113). For AC009509.2, the AUC was 0.710 (95% CI 0.599-0.822, P=0.0005). Bioinformatic methods (GO enrichment, AS analysis and lncRNA-mRNA network construction) were performed to reveal the role of lncRNAs.

CONCLUSIONS

This study discussed differentially expressed lncRNA and their potential interaction with mRNA in AF. LncRNA AC009509.2 could be a new potential biomarker for AF prediction.

摘要

背景

心房颤动(AF)是导致中风和心力衰竭等严重疾病的最常见心律失常之一。最近的研究表明,长非编码 RNA(lncRNA)与心血管疾病有关。然而,AF 的分子机制尚不完全清楚。本研究旨在发现与对照组相比在 AF 中差异表达的 lncRNA,并评估这些 lncRNA 的潜在功能。

方法

本研究纳入了 97 名患者(49 名 AF 患者和 48 名非 AF 患者)。其中,3 名 AF 患者和 3 名对照的白细胞悬液被送去进行 RNA-seq 分析,以选择差异表达的 lncRNA 和 mRNA。在另一批样本(46 名 AF 患者和 45 名对照)中验证了不同的 lncRNA 表达。进行基因本体(GO)富集分析以注释选定 mRNAs 的功能。进行可变剪接(AS)分析并构建 lncRNA-mRNA 网络。使用接收器操作特征(ROC)曲线评估诊断价值。利用逻辑回归分析评估 AF 的风险或保护因素。

结果

与对照组相比,AF 患者中检测到 223 个 mRNAs 和 105 个 lncRNAs。通过定量实时 PCR(qRT-PCR)在另一批样本中验证了与 AF 相关的 4 个 lncRNA(LINC01781、AC009509.2、AL662844.3、AL662844.4),发现 AF 患者中 AC009509.2 上调,LINC01781 下调。多变量逻辑回归分析表明,左心房直径(OR 1.201;95%CI 1.093-1.320;P=0.000)和 AC009509.2(OR 1.732;95%CI 1.092-2.747;P=0.020)与 AF 相关。ROC 曲线表明,AC009509.2、LINC01781 和左心房直径(LAD)是 AF 的预测因子。对于 LINC01781,曲线下面积(AUC)为 0.654(95%CI 0.541-0.767,P=0.0113)。对于 AC009509.2,AUC 为 0.710(95%CI 0.599-0.822,P=0.0005)。通过生物信息学方法(GO 富集、AS 分析和 lncRNA-mRNA 网络构建)揭示了 lncRNA 的作用。

结论

本研究探讨了 AF 中差异表达的 lncRNA 及其与 mRNA 的潜在相互作用。lncRNA AC009509.2 可能是 AF 预测的一个新的潜在生物标志物。

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