Author + information
- Yanmei Chen,
- Xinzhong Li,
- Guojun Chen,
- Lintao Zhong,
- Xiang He,
- Chixiong Huang,
- Bing Li,
- Hairui Li,
- Shifei Wang,
- Yuanwen Jing and
- Jianping Bin
Background: In response to injury, adult human heart has limited regeneration capacity and progression to heart failure, while fetal heart has robust regenerative capacity. Long non-coding RNAs (IncRNAs) have been implicated in cardiac development or heart failure, but little is known about the role of human lncRNAs in endogenous cardiac regeneration. In this study, we aimed to characterize lncRNA transcriptome between human fetal and adult hearts and to elucidate their potential roles in endogenous cardiac regeneration.
Methods: A genome-wide analysis of quantitative RNA sequencing data from four normal human fetal and adult hears were performed. Immunofluorescence staining were used to detect cardiomyocytes(CM) proliferation. To evaluate remodeling after myocardial infarction (MI), triphenyltetrazolium chloride staining, masson's trichrome staining and echocardiography were performed. Pull-down assays and masss pectrometry were conducted to search for lncPTTG1 interacting proteins.
Results: We detected 3789 mRNAs and 3092 lncRNAs differentially expressed between fetal and adult heart. Functional analysis revealed that the up-regulated mRNAs and up-regulated lncRNA:cis-mRNA pairs were associated with cell cycle. Both network analysis and motif analysis suggested a fetal up-regulated lncRNA (lncPTTG1) involved in endogenous cardiac regeneration. In both vitro and in vivo, over-expression of lncPTTG1 promoted CM proliferation. After MI in adult rat, lncPTTG1 stimulated CM proliferation and improved post-MI remodeling. RNA pull-down assays and masss pectrometry indicated that mitotic centromere-associated kinesin (MCAK) was interacted with lncPTTG1. Subsequently, lncPTTG1 bound directly to MCAK in the cytoplasm, which prevented MCAK phosphorylationon. Knocked down MCAK counteracted the promoting effect of lncPTTG1 on CM proliferation.
Conclusions: We provided lncRNA profiles in human fetal-to-adult heart transition and showed that fetal up-regulated lncPTTG1 promoted CM proliferation, trigger endogenous cardiac regeneration and attenuated post-MI remodeling by directly interacting with MCAK and regulating its posttranslational modification.
Moderated Poster Contributions
Heart Failure and Cardiomyopathies Moderated Poster Theater, Poster Hall, Hall C
Saturday, March 18, 2017, 1:00 p.m.-1:10 p.m.
Session Title: Put Your Codon! Genetic Insights Into Heart Failure
Abstract Category: 12. Heart Failure and Cardiomyopathies: Basic
Presentation Number: 1226M-07
- 2017 American College of Cardiology Foundation