Integrated Analysis of Dysregulated lncRNA Expression in Fetal Cardiac Tissues with Ventricular Septal Defect

Guixian Song,Guixian Song,Shasha Zhu,Shasha Zhu,Yahui Shen,Yahui Shen,Ming Liu,Ming Liu,Jingai Zhu,Lingmei Qian,Zhangbin Yu,Zhangbin Yu,Xiangqing Kong,Xiangqing Kong,Hailang Liu,Hailang Liu,Jingai Zhu,Ya-Qing Shen

doi:10.1371/journal.pone.0077492

Abstract

Ventricular septal defects (VSD) are the most common form of congenital heart disease, which is the leading non-infectious cause of death in children; nevertheless, the exact cause of VSD is not yet fully understood. Long non-coding RNAs (lncRNAs) have been shown to play key roles in various biological processes, such as imprinting control, circuitry controlling pluripotency and differentiation, immune responses and chromosome dynamics. Notably, a growing number of lncRNAs have been implicated in disease etiology, although an association with VSD has not been reported. In the present study, we conducted an integrated analysis of dysregulated lncRNAs, focusing specifically on the identification and characterization of lncRNAs potentially involving in initiation of VSD. Comparison of the transcriptome profiles of cardiac tissues from VSD-affected and normal hearts was performed using a second-generation lncRNA microarray, which covers the vast majority of expressed RefSeq transcripts (29,241 lncRNAs and 30,215 coding transcripts). In total, 880 lncRNAs were upregulated and 628 were downregulated in VSD. Furthermore, our established filtering pipeline indicated an association of two lncRNAs, ENST00000513542 and RP11-473L15.2, with VSD. This dysregulation of the lncRNA profile provides a novel insight into the etiology of VSD and furthermore, illustrates the intricate relationship between coding and ncRNA transcripts in cardiac development. These data may offer a background/reference resource for future functional studies of lncRNAs related to VSD.

Highlights

The heart is extraordinary, in its complex ontogeny, architecture and uninterrupted contractility, and in its ability to respond acutely to changing physiological and neuropsychological circumstances
By comparing the transcriptome profiles of Ventricular septal defects (VSD)-affected cardiac and normal tissues using the microarray technique, we have generated an integrated analysis of dysregulated Long noncoding RNAs (lncRNAs), focusing on the identification and characterization of potential lncRNAs involved in the initiation of VSD
We recovered the vast majority of expressed RefSeq transcripts; 3,045 lncRNAs and 30,215 coding transcripts were detectable using this secondgeneration LncRNA microarray

Summary

Introduction

The heart is extraordinary, in its complex ontogeny, architecture and uninterrupted contractility, and in its ability to respond acutely to changing physiological and neuropsychological circumstances. Heart development requires precise temporal and spatial regulation of gene expression, in which the highly conserved modulation networks of transcription factors accurately control the signaling pathways required for normal cardiovascular development. The regulatory networks that control the development and adaptations of the heart have been under intense investigation[2]. Emphasis is being placed on elucidating the complex interplay between the many hierarchical levels of gene regulation that give a network its dynamic properties and arranges cells into a myriad of precisely sculpted three-dimensional tissues and interacting organ systems. Several transcription factors (TFs) such as NKX2.5[3], Tbx5[4] and GATA4[5], have been identified as being essential for heart development. The upstream regulators as well as interacting partners and downstream targets/effectors of the handful of TFs known so far to be linked to human CHD, remain largely unknown

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Conclusion