Abstract

// Zhibing Qiu 1, * , Bin Ye 2, * , Li Yin 1 , Wen Chen 1 , Yueyue Xu 1 and Xin Chen 1 1 Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China 2 Department of Anesthesiology, Yangzhou Maternal and Child Health Hospital, Yangzhou 225002, Jiangsu Province, China * These authors have contributed equally to this work Correspondence to: Xin Chen, email: chenxinCX66@163.com Keywords: dilated cardiomyopathy; differentially expressed gene; lncRNA; Weighted Gene Coexpression Network Analysis Abbreviations: DCM: dilated cardiomyopathy; DEGs: differentially expressed genes; DELs: DE lncRNAs; WGCNA: Weighted Gene Coexpression Network Analysis Received: September 30, 2017 Accepted: December 05, 2017 Published: January 02, 2018 ABSTRACT Purpose: This study aimed to explore lncRNAs implicated in dilated cardiomyopathy (DCM) using high-throughput sequencing. Methods: From February 2016 to May 2017, ten samples of failing hearts collected from the left ventricles of DCM patients undergoing heart transplants, and ten control samples obtained from normal heart donors were included in this study. After sequencing, raw data were processed, and differentially expressed genes (DEGs) and lncRNAs between samples from patients with DCM and controls were screened, followed by functional enrichment analysis and Weighted Gene Coexpression Network Analysis (WGCNA). Five key lncNRAs were validated through real-time PCR. Results: After processing sequence data, 1398 DEGs were identified between DCM and control groups, including 267 lncRNAs. WGCNA identified seven modules that were significantly correlated with DCM. The top 50 genes in the three modules (black, dark-green, and green-yellow) were significantly correlated with the DCM disease state. Four core enrichment lncRNAs, such as AC061961.2, LINGO1-AS1, and RP11-557H15.4, in the green-yellow module were associated with functions of neurotransmitter secretion. Five core enrichment lncRNAs, such as KB-1299A7.2 and RP11-13E1.5, in the black module co-regulated functions associated with the regulation of blood circulation and heart contraction. AC061961.2, LINGO1-AS1, and RP11-13E1.5 were confirmed to be downregulated in DCM tissues by real-time PCR. Conclusion: The present study suggests that downregulation of AC061961.2, LINGO1-AS1, and RP11-13E1.5 is associated with DCM progression, and these may serve as key diagnostic biomarkers and therapeutic targets for DCM.

Highlights

  • Cardiomyopathies are a group of heart muscle diseases characterized by abnormal chamber size and wall thickness or abnormal contractile function [1]

  • After processing sequence data, 1398 differentially expressed genes (DEGs) were identified between Dilated cardiomyopathy (DCM) and control groups, including 267 long non-coding RNAs (lncRNAs)

  • Weighted Gene Coexpression Network Analysis (WGCNA) identified seven modules that were significantly correlated with DCM

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Summary

Introduction

Cardiomyopathies are a group of heart muscle diseases characterized by abnormal chamber size and wall thickness or abnormal contractile function [1]. Dilated cardiomyopathy (DCM) is the most common cardiomyopathy worldwide, characterized by enlargement in left ventricular cavity, as well as impaired contractility in the absence of significant coronary artery disease [2]. Some abnormal loading conditions, including primary valvular diseases, congenital heart diseases and arterial hypertension may result in DCM. DCM may lead to sudden cardiac death and progressive heart failure and is related to serious morbidity and premature mortality [3]. The 5-year mortality for DCM remains up to 20% [4]. Studies have found that genetic etiologies are www.impactjournals.com/oncotarget s363

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