Identification of miRNA–mRNA–TFs Regulatory Network and Crucial Pathways Involved in Tetralogy of Fallot
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. However, its pathogenesis remains unknown. To explore key regulatory connections and crucial pathways underlying the TOF, gene or microRNA expression profile datasets of human TOF were obtained from the National Center f...
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| Format: | Article |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2020.00552/full |
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| author | Guoling You Guoling You Bailing Zu Bo Wang Qihua Fu Fen Li |
| author_facet | Guoling You Guoling You Bailing Zu Bo Wang Qihua Fu Fen Li |
| author_sort | Guoling You |
| collection | DOAJ |
| description | Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. However, its pathogenesis remains unknown. To explore key regulatory connections and crucial pathways underlying the TOF, gene or microRNA expression profile datasets of human TOF were obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRs) between TOF and healthy groups were identified after data preprocessing, followed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, we further constructed protein–protein interaction (PPI) network and subnetwork of modules. Ultimately, to investigate the regulatory network underlying TOF, a global triple network including miRNAs, mRNAs, and transcription factors (TFs) was constructed based on the integrated data. In the present study, a total of 529 DEmRNAs, including 115 downregulated and 414 upregulated DEmRNAs, and 7 significantly upregulated DemiRs, including miR-499, miR-23b, miR-222, miR-1275, miR-93, miR-155, and miR-187, were found between TOF and control groups. Furthermore, 22 hub genes ranked by top 5% genes with high connectivity and six TFs, including SRF, CNOT4, SIX6, SRRM3, NELFA, and ONECUT3, were identified and might play crucial roles in the molecular pathogenesis of TOF. Additionally, an miRNA–mRNA–TF co-regulatory network was established and indicated ubiquitin-mediated proteolysis, energy metabolism associated pathways, neurodevelopmental disorder associated pathways, and ribosomes might be involved in the pathogenesis of TOF. The current research provides a comprehensive perspective of regulatory mechanism networks underlying TOF and also identifies potential molecule targets of genetic counseling and prenatal diagnosis for TOF. |
| first_indexed | 2024-12-10T04:40:00Z |
| format | Article |
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| language | English |
| last_indexed | 2024-12-10T04:40:00Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-b54b588a37bd42f6a360f2529ba414bc2022-12-22T02:01:55ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-06-011110.3389/fgene.2020.00552524515Identification of miRNA–mRNA–TFs Regulatory Network and Crucial Pathways Involved in Tetralogy of FallotGuoling You0Guoling You1Bailing Zu2Bo Wang3Qihua Fu4Fen Li5Department of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaTetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. However, its pathogenesis remains unknown. To explore key regulatory connections and crucial pathways underlying the TOF, gene or microRNA expression profile datasets of human TOF were obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRs) between TOF and healthy groups were identified after data preprocessing, followed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, we further constructed protein–protein interaction (PPI) network and subnetwork of modules. Ultimately, to investigate the regulatory network underlying TOF, a global triple network including miRNAs, mRNAs, and transcription factors (TFs) was constructed based on the integrated data. In the present study, a total of 529 DEmRNAs, including 115 downregulated and 414 upregulated DEmRNAs, and 7 significantly upregulated DemiRs, including miR-499, miR-23b, miR-222, miR-1275, miR-93, miR-155, and miR-187, were found between TOF and control groups. Furthermore, 22 hub genes ranked by top 5% genes with high connectivity and six TFs, including SRF, CNOT4, SIX6, SRRM3, NELFA, and ONECUT3, were identified and might play crucial roles in the molecular pathogenesis of TOF. Additionally, an miRNA–mRNA–TF co-regulatory network was established and indicated ubiquitin-mediated proteolysis, energy metabolism associated pathways, neurodevelopmental disorder associated pathways, and ribosomes might be involved in the pathogenesis of TOF. The current research provides a comprehensive perspective of regulatory mechanism networks underlying TOF and also identifies potential molecule targets of genetic counseling and prenatal diagnosis for TOF.https://www.frontiersin.org/article/10.3389/fgene.2020.00552/fullcongenital heart diseasedifferential expression genesmicroRNAsregulatory networksTetralogy of Fallot |
| spellingShingle | Guoling You Guoling You Bailing Zu Bo Wang Qihua Fu Fen Li Identification of miRNA–mRNA–TFs Regulatory Network and Crucial Pathways Involved in Tetralogy of Fallot Frontiers in Genetics congenital heart disease differential expression genes microRNAs regulatory networks Tetralogy of Fallot |
| title | Identification of miRNA–mRNA–TFs Regulatory Network and Crucial Pathways Involved in Tetralogy of Fallot |
| title_full | Identification of miRNA–mRNA–TFs Regulatory Network and Crucial Pathways Involved in Tetralogy of Fallot |
| title_fullStr | Identification of miRNA–mRNA–TFs Regulatory Network and Crucial Pathways Involved in Tetralogy of Fallot |
| title_full_unstemmed | Identification of miRNA–mRNA–TFs Regulatory Network and Crucial Pathways Involved in Tetralogy of Fallot |
| title_short | Identification of miRNA–mRNA–TFs Regulatory Network and Crucial Pathways Involved in Tetralogy of Fallot |
| title_sort | identification of mirna mrna tfs regulatory network and crucial pathways involved in tetralogy of fallot |
| topic | congenital heart disease differential expression genes microRNAs regulatory networks Tetralogy of Fallot |
| url | https://www.frontiersin.org/article/10.3389/fgene.2020.00552/full |
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