通过综合分析与心脏发育相关的 lncRNA 和 mRNA，筛选对心肌细胞增殖至关重要的 lncRNA。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2024-10-01 DOI:10.1016/j.yexcr.2024.114277

Hanqing Luo , Hoshun Chong , Yapeng Wang , Yaxuan Gao , Wei Xie , Dongjin Wang

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引用次数: 0

摘要

背景：哺乳动物心肌细胞的增殖潜力在出生后不久就会明显下降。在心脏发育过程中，长非编码 RNA（lncRNA）和 mRNA 的表达模式都发生了改变。然而，人们对 lncRNAs 在心肌细胞细胞周期停滞中的作用仍缺乏足够的了解：方法：分析了出生后第 1、7 和 28 天表现出不同再生潜能的小鼠心脏中 lncRNAs 和 mRNAs 的表达模式。采用加权相关网络分析（WGCNA）来阐明lncRNA和mRNA之间的共表达关系。利用 STRING 数据库建立了蛋白质-蛋白质相互作用（PPI）网络，并利用 CytoHubba 鉴定了中心 lncRNA。分子复合体检测（MCODE）用于在Cytoscape中筛选PPI网络的核心模块。利用 miRTarBase 和 AnnoLnc2 分别预测了可能调控 mRNA 的上游 lncRNA 和 miRNA。通过结扎左前降支冠状动脉诱发心肌梗死（MI）：与P1心脏相比，P7心脏中有618个mRNA和414个lncRNA发生了转录变化，而从P7到P28则有2358个mRNA和1290个lncRNA发生了转录变化。基因本体（GO）分析表明，两组比较中的模块1都富含有丝分裂细胞周期过程。2810408I11Rik和2010110K18Rik被鉴定为中枢lncRNA，它们对心肌细胞增殖的影响在体外得到了验证。此外，还预测了四种lncRNA-miRNA-mRNA调控轴，以解释2810408I11Rik和2010110K18Rik调控心肌细胞增殖的机制。值得注意的是，2810408I11Rik的过表达能增强心肌梗死后成人心脏的心肌细胞增殖和心脏再生：本研究系统分析了P1、P7和P28期的lncRNAs和mRNAs。这些发现可能会加深我们对心脏发育框架的理解，并对心脏再生产生重要影响。

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Screening lncRNAs essential for cardiomyocyte proliferation by integrative profiling of lncRNAs and mRNAs associated with heart development

Background

The proliferation potential of mammalian cardiomyocytes declines markedly shortly after birth. Both long non-coding RNAs (lncRNAs) and mRNAs demonstrate altered expression patterns during cardiac development. However, the role of lncRNAs in the cell cycle arrest of cardiomyocytes remains inadequately understood.

Method

The expression pattern of lncRNAs and mRNAs was analyzed in mouse hearts exhibiting varying regenerative potentials on postnatal days (P) 1, 7, and 28. Weighted correlation network analysis (WGCNA) was employed to elucidate the co-expression relationship between lncRNAs and mRNAs. Protein-protein interaction (PPI) network was built using the STRING database, and hub lncRNAs were identified by CytoHubba. Molecular Complex Detection (MCODE) was used to screen core modules of the PPI network in Cytoscape. Upstream lncRNAs and miRNAs which may regulate mRNAs were predicted using miRTarBase and AnnoLnc2, respectively. Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery.

Results

Compared with the P1 heart, 618 mRNAs and 414 lncRNAs displayed.

transcriptional changes in the P7 heart, while 2358 mRNAs and 1290 lncRNAs showed from P7 to P28. Gene Ontology (GO) analysis revealed that module 1 in the both comparisons was enriched in the mitotic cell cycle process. 2810408I11Rik and 2010110K18Rik were identified as hub lncRNAs and their effects on the proliferation of cardiomyocytes were verified in vitro. Additionally, four lncRNA-miRNA-mRNA regulatory axes were predicted to explain the mechanism by which 2810408I11Rik and 2010110K18Rik regulate cardiomyocyte proliferation. Notably, the overexpression of 2810408I11Rik enhances cardiomyocyte proliferation and heart regeneration in the adult heart following MI.

Conclusion

This study systematically analyzed the landscape of lncRNAs and mRNAs at P1, P7, and P28. These findings may enhance our understanding of the framework for heart development and could have significant implications for heart regeneration.

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.