Data_Sheet_1_Cardiac Regeneration and Tumor Growth—What Do They Have in Common?.PDF

Acute myocardial infarction is a leading cause of death. Unlike most adult mammals, zebrafish have the capability to almost fully regenerate their hearts after injury. In contrast, ischemic damage in adult human and mouse hearts usually results in scar tissue. mRNA-Sequencing (Seq) and miRNA-Seq analyses of heart regeneration in zebrafish over time showed that the process can be divided into three phases: the first phase represents dedifferentiation and proliferation of cells, the second phase is characterized by migration, and in the third phase cell signals indicate heart development and differentiation. The first two phases seem to share major similarities with tumor development and growth. To gain more insight into these similarities between cardiac regeneration and tumor development and growth, we used patient matched tumor normal (“healthy”) RNA-Seq data for several tumor entities from The Cancer Genome Atlas (TCGA). Subsequently, RNA data were processed using the same pipeline for both the zebrafish samples and tumor datasets. Functional analysis showed that multiple Gene Ontology terms (GO terms) are involved in both early stage cardiac regeneration and tumor development/growth across multiple tumor entities. These GO terms are mostly associated with cell cycle processes. Further analysis showed that orthologous genes are the same key players that regulated these changes in both diseases. We also observed that GO terms associated with heart development in the third late phase of cardiac regeneration are downregulated in the tumor entities. Taken together, our analysis illustrates similarities between cardiac remodeling and tumor progression.

急性心肌梗死是导致死亡的主要原因。与大多数成年哺乳动物不同，斑马鱼在受伤后几乎能够完全再生心脏。相比之下，成年人类和鼠类心脏的缺血性损伤通常会导致瘢痕组织的形成。对斑马鱼心脏再生的mRNA测序（Seq）和miRNA测序分析显示，该过程可分为三个阶段：第一阶段代表细胞的去分化和增殖；第二阶段以细胞的迁移为特征；在第三阶段，细胞信号指示心脏的发育和分化。前两个阶段似乎与肿瘤的发生和生长存在主要相似之处。为了深入了解心脏再生与肿瘤发生和生长之间的相似性，我们使用了来自癌症基因组图谱（TCGA）中多个肿瘤实体的患者匹配肿瘤正常（“健康”）RNA-Seq数据。随后，对斑马鱼样本和肿瘤数据集的RNA数据进行相同的处理流程。功能分析表明，多个基因本体术语（GO术语）涉及多个肿瘤实体中的早期心脏再生和肿瘤发展/生长。这些GO术语大多与细胞周期过程相关。进一步分析显示，直系同源基因是调控这两种疾病中变化的关键参与者。我们还观察到，与心脏再生第三阶段晚期的心脏发育相关的GO术语在肿瘤实体中下调。综上所述，我们的分析描绘了心脏重塑与肿瘤进展之间的相似性。