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鉴定糖尿病心肌病的枢纽基因和潜在 ceRNA 网络。

Identification of hub genes and potential ceRNA networks of diabetic cardiomyopathy.

机构信息

Department of Cardiology, The Third People's Hospital of Chengdu/Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China.

School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China.

出版信息

Sci Rep. 2023 Jun 24;13(1):10258. doi: 10.1038/s41598-023-37378-5.

Abstract

Diabetic cardiomyopathy (DCM), a common complication of diabetes, is defined as ventricular dysfunction in the absence of underlying heart disease. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), play a crucial role in the development of DCM. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify key modules in DCM-related pathways. DCM-related miRNA-mRNA network and DCM-related ceRNA network were constructed by miRNA-seq to identify hub genes in these modules. We identified five hub genes that are associated with the onset of DCM, including Troponin C1 (Tnnc1), Phospholamban (Pln), Fatty acid binding proteins 3 (Fabp3), Popeye domain containing 2 (Popdc2), and Tripartite Motif-containing Protein 63 (Trim63). miRNAs that target the hub genes were mainly involved in TGF-β and Wnt signaling pathways. GO BP enrichment analysis found these miRNAs were involved in the signaling of TGF-β and glucose homeostasis. Q-PCR results found the gene expressions of Pln, Fabp3, Trim63, Tnnc1, and Popdc2 were significantly increased in DCM. Our study identified five hub genes (Tnnc1, Pln, Fabp3, Popdc2, Trim63) whose associated ceRNA networks are responsible for the onset of DCM.

摘要

糖尿病心肌病(DCM)是糖尿病的一种常见并发症,定义为在不存在潜在心脏病的情况下出现心室功能障碍。非编码 RNA(ncRNA),包括长非编码 RNA(lncRNA)和 microRNA(miRNA),在 DCM 的发展中起着至关重要的作用。加权基因共表达网络分析(WGCNA)用于鉴定 DCM 相关途径中的关键模块。通过 miRNA-seq 构建 DCM 相关 miRNA-mRNA 网络和 DCM 相关 ceRNA 网络,以鉴定这些模块中的枢纽基因。我们鉴定了五个与 DCM 发病相关的枢纽基因,包括肌钙蛋白 C1(Tnnc1)、肌浆球蛋白结合蛋白(Pln)、脂肪酸结合蛋白 3(Fabp3)、Popeye 结构域包含蛋白 2(Popdc2)和三联基序蛋白 63(Trim63)。靶向这些枢纽基因的 miRNA 主要参与 TGF-β 和 Wnt 信号通路。GO BP 富集分析发现这些 miRNA 参与 TGF-β 和葡萄糖稳态的信号转导。Q-PCR 结果发现 DCM 中 Pln、Fabp3、Trim63、Tnnc1 和 Popdc2 的基因表达显著增加。我们的研究鉴定了五个枢纽基因(Tnnc1、Pln、Fabp3、Popdc2、Trim63),其相关的 ceRNA 网络负责 DCM 的发病。

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