Oncotarget

Research Papers:

Dysregulated long intergenic non-coding RNA modules contribute to heart failure

Lin Pang, Jing Hu, Guanxiong Zhang, Xiang Li, Xinxin Zhang, Fulong Yu, Yujia Lan, Jinyuan Xu, Bo Pang, Dong Han, Yun Xiao and Xia Li _

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Oncotarget. 2016; 7:59676-59690. https://doi.org/10.18632/oncotarget.10834

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Abstract

Lin Pang1,*, Jing Hu1,*, Guanxiong Zhang1,*, Xiang Li1,*, Xinxin Zhang1, Fulong Yu1, Yujia Lan1, Jinyuan Xu1, Bo Pang2, Dong Han3, Yun Xiao1,4, Xia Li1

1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China

2Department of Genetics, Harbin Medical University, Harbin, Heilongjiang, China

3National Center for Nanoscience and Technology, Haidian, Beijing, China

4Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang, China

*These authors have contributed equally to this work

Correspondence to:

Xia Li, email: lixia@hrbmu.edu.cn

Yun Xiao, email: xiaoyun@ems.hrbmu.edu.cn

Dong Han, email: dhan@nanoctr.cn

Keywords: lincRNAmodule, heart failure, ceRNA, contraction, heart specificity

Received: March 01, 2016    Accepted: July 09, 2016    Published: July 25, 2016

ABSTRACT

Long intergenic non-coding RNAs (lincRNAs) are emerging as important regulatory molecules involved in diseases including heart failure. However, little is known about how the lincRNAs work together with protein-coding genes (PCGs) contributing to the pathogenesis of heart failure. In this study, we constructed a comprehensive transcriptome profile of lincRNAs, PCGs and miRNAs using RNA-seq and miRNA-seq data of 16 heart failure patients (HFs) and 8 non-failing individuals (NFs). Through integrating lincRNA and PCG expression profiles, we identified HF-associated lincRNA modules. We identified a heart-specific lincRNA module which was significantly enriched for differentially expressed lincRNAs and PCGs. This module was associated with heart failure rather than with other clinical traits such as sex, age, smoking and diabetes mellitus. Moreover, the module was significantly correlated with certain indicators of left ventricular function like ejection fraction and left ventricular end-diastolic diameter, implying the potential of its components as crucial biomarkers. Apart from enhancer-like function, lincRNAs in this module could act as competing endogenous RNAs (ceRNAs) to regulate genes which were associated with left-ventricular systolic function. Our work provided deep insights into the critical roles of lincRNAs in the pathology of heart failure and suggested that they could be valuable biomarkers and therapeutic targets.


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