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

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.

SUBMITTER: Hou J

PROVIDER: S-EPMC10290640 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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

Hou Jun J Liang Wan Yi WY Xiong Shiqiang S Long Pan P Yue Tian T Wen Xudong X Wang Tianchen T Deng Haoyu H

Scientific reports 20230624 1

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 hu ...[more]

PMID: 37355664

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Project description:BackgroundDiabetic nephropathy (DN) is the major cause of end-stage renal disease worldwide. The mechanism of tubulointerstitial lesions in DN is not fully elucidated. This article aims to identify novel genes and clarify the molecular mechanisms for the progression of DN through integrated bioinformatics approaches.MethodWe downloaded microarray datasets from Gene Expression Omnibus (GEO) database and identified the differentially expressed genes (DEGs). Enrichment analyses, construction of Protein-protein interaction (PPI) network, and visualization of the co-expressed network between mRNAs and microRNAs (miRNAs) were performed. Additionally, we validated the expression of hub genes and analyzed the Receiver Operating Characteristic (ROC) curve in another GEO dataset. Clinical analysis and ceRNA networks were further analyzed.ResultsTotally 463 DEGs were identified, and enrichment analyses demonstrated that extracellular matrix structural constituents, regulation of immune effector process, positive regulation of cytokine production, phagosome, and complement and coagulation cascades were the major enriched pathways in DN. Three hub genes (CD53, CSF2RB, and LAPTM5) were obtained, and their expression levels were validated by GEO datasets. Pearson analysis showed that these genes were negatively correlated with the glomerular filtration rate (GFR). After literature searching, the ceRNA networks among circRNAs/IncRNAs, miRNAs, and mRNAs were constructed. The predicted RNA pathway of NEAT1/XIST-hsa-miR-155-5p/hsa-miR-486-5p-CSF2RB provides an important perspective and insights into the molecular mechanism of DN.ConclusionIn conclusion, we identified three genes, namely CD53, CSF2RB, and LAPTM5, as hub genes of tubulointerstitial lesions in DN. They may be closely related to the pathogenesis of DN and the predicted RNA regulatory pathway of NEAT1/XIST-hsa-miR-155-5p/hsa-miR-486-5p-CSF2RB presents a biomarker axis to the occurrence and development of DN.

Dataset Information

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

Publications

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

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