Microarray analysis reveals a potential role of LncRNAs expression in cardiac cell proliferation.

Jue Wang,Maoping Chu,Chengchao Sun,Ming Li,Xueli Cai,Zhimin Geng,Jiakan Weng,Longjie Shen

doi:10.1186/s12861-016-0139-4

Abstract

BackgroundLong non-coding RNAs (LncRNAs) have been identified to play important roles in epigenetic processes that underpin organogenesis. However, the role of LncRNAs in the regulation of transition from fetal to adult life of human heart has not been evaluated.MethodsImmunofiuorescent staining was used to determine the extent of cardiac cell proliferation. Human LncRNA microarrays were applied to define gene expression signatures of the fetal (13–17 weeks of gestation, n = 4) and adult hearts (30–40 years old, n = 4). Pathway analysis was performed to predict the function of differentially expressed mRNAs (DEM). DEM related to cell proliferation were selected to construct a lncRNA-mRNA co-expression network. Eight lncRNAs were confirmed by quantificational real-time polymerase chain reaction (n = 6).ResultsCardiac cell proliferation was significant in the fetal heart. Two thousand six hundred six lncRNAs and 3079 mRNAs were found to be differentially expressed. Cell cycle was the most enriched pathway in down-regulated genes in the adult heart. Eight lncRNAs (RP11-119 F7.5, AX747860, HBBP1, LINC00304, TPTE2P6, AC034193.5, XLOC_006934 and AL833346) were predicted to play a central role in cardiac cell proliferation.ConclusionsWe discovered a profile of lncRNAs differentially expressed between the human fetal and adult heart. Several meaningful lncRNAs involved in cardiac cell proliferation were disclosed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-016-0139-4) contains supplementary material, which is available to authorized users.

Highlights

Long non-coding RNAs (LncRNAs) have been identified to play important roles in epigenetic processes that underpin organogenesis
Ki-67 has been reported to be detected in proliferating cells at all active phases of cell cycle while cTnT is a cardiomyocyte marker that expresses in both cycling and non-cycling cells
Ki-67 stained cells were observed in fetal heart (Fig. 1a), not in adult heart (Fig. 1b), proving that the cardiac cell proliferation only occurred in fetal heart

Summary

Introduction

Long non-coding RNAs (LncRNAs) have been identified to play important roles in epigenetic processes that underpin organogenesis. The role of LncRNAs in the regulation of transition from fetal to adult life of human heart has not been evaluated. 10 weeks after fertilization, four important processes, namely, looping, trabeculation, septation and myocardial compaction, have been completed in the human fetal heart. Previous studies have elucidated that the architecture of LncRNAs are long non-coding RNAs, which can function as either primary or spliced transcripts, and they are independent of the currently known classes of small. It has been reported that lncRNAs can impact gene expression at multiple levels (e.g., transcriptional and post-transcriptional control, epigenetic regulation). LncRNAs have been found to be able to regulate the expressions of proximal and distal protein-coding genes through cis- and trans-acting mechanisms [10]. Many lncRNAs have been identified in humans, which prompt the building of human lncRNA database providing expression profiles of lncRNAs [11]

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Conclusion