Identification and analysis of mitochondria-related key genes of heart failure
Abstract Mitochondria-induced cell death is a vital mechanism of heart failure (HF). Thus, identification of mitochondria-related genes (Mito-RGs) based on transcriptome sequencing data of HF might provide novel diagnostic markers and therapeutic targets for HF. First, bioinformatics analysis was co...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03605-2 |
| _version_ | 1811211598496268288 |
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| author | Haozhen Yu Mujun Yu Zhuang Li Enhu Zhang Heng Ma |
| author_facet | Haozhen Yu Mujun Yu Zhuang Li Enhu Zhang Heng Ma |
| author_sort | Haozhen Yu |
| collection | DOAJ |
| description | Abstract Mitochondria-induced cell death is a vital mechanism of heart failure (HF). Thus, identification of mitochondria-related genes (Mito-RGs) based on transcriptome sequencing data of HF might provide novel diagnostic markers and therapeutic targets for HF. First, bioinformatics analysis was conducted on the GSE57338, GSE76701, GSE136547, and GSE77399 datasets in the Gene Expression Omnibus. Next, we analyzed HF-Mito differentially expressed genes (DEGs) using the protein–protein interaction (PPI) network for obtaining critical genes and exploring their functions. Subsequently, immune cell scores of the HF and normal groups were compared. The potential alteration mechanisms of the key genes were investigated by constructing a competing endogenous RNA network. Finally, we predicted potential therapeutic agents and validated the expression levels of the key genes. Twenty-three HF-Mito DEGs were acquired in the GSE57338 dataset, and the PPI network obtained four key genes, including IFIT3, XAF1, RSAD2, and MX1. According to gene set enrichment analysis, the key genes showed high enrichment in myogenesis and hypoxia. Immune cell analysis demonstrated that aDCs, B cells, and 20 other immune cell types varied between the HF and normal groups. Moreover, we observed that H19 might affect the expression of IFIT3, AXF1, and RSAD2. PCGEM1 might regulate RSAD2 expression. A total of 515 potential therapeutic drugs targeting the key genes, such as tretinoin, silicon dioxide, and bisphenol A, were acquired. Finally, IFIT3, RSAD2, and MX1 expression increased in HF samples compared with normal samples in the GSE76701 dataset, conforming to the GSE57338 dataset analysis. This work screened four key genes, namely, IFIT3, XAF1, RSAD2, and MX1, which can be further explored in subsequent studies for their specific molecular mechanisms in HF. |
| first_indexed | 2024-04-12T05:15:24Z |
| format | Article |
| id | doaj.art-f63007ae43554958befb8f7df513ad46 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T05:15:24Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-f63007ae43554958befb8f7df513ad462022-12-22T03:46:39ZengBMCJournal of Translational Medicine1479-58762022-09-0120111210.1186/s12967-022-03605-2Identification and analysis of mitochondria-related key genes of heart failureHaozhen Yu0Mujun Yu1Zhuang Li2Enhu Zhang3Heng Ma4School of Basic Medical Sciences, Shaanxi University of Chinese MedicineSchool of Life Sciences, Yan’an UniversitySchool of Basic Medical Sciences, Shaanxi University of Chinese MedicineSchool of Basic Medical Sciences, Shaanxi University of Chinese MedicineDepartment of Physiology and Pathophysiology, School of Basic Medicine, Fourth Military Medical UniversityAbstract Mitochondria-induced cell death is a vital mechanism of heart failure (HF). Thus, identification of mitochondria-related genes (Mito-RGs) based on transcriptome sequencing data of HF might provide novel diagnostic markers and therapeutic targets for HF. First, bioinformatics analysis was conducted on the GSE57338, GSE76701, GSE136547, and GSE77399 datasets in the Gene Expression Omnibus. Next, we analyzed HF-Mito differentially expressed genes (DEGs) using the protein–protein interaction (PPI) network for obtaining critical genes and exploring their functions. Subsequently, immune cell scores of the HF and normal groups were compared. The potential alteration mechanisms of the key genes were investigated by constructing a competing endogenous RNA network. Finally, we predicted potential therapeutic agents and validated the expression levels of the key genes. Twenty-three HF-Mito DEGs were acquired in the GSE57338 dataset, and the PPI network obtained four key genes, including IFIT3, XAF1, RSAD2, and MX1. According to gene set enrichment analysis, the key genes showed high enrichment in myogenesis and hypoxia. Immune cell analysis demonstrated that aDCs, B cells, and 20 other immune cell types varied between the HF and normal groups. Moreover, we observed that H19 might affect the expression of IFIT3, AXF1, and RSAD2. PCGEM1 might regulate RSAD2 expression. A total of 515 potential therapeutic drugs targeting the key genes, such as tretinoin, silicon dioxide, and bisphenol A, were acquired. Finally, IFIT3, RSAD2, and MX1 expression increased in HF samples compared with normal samples in the GSE76701 dataset, conforming to the GSE57338 dataset analysis. This work screened four key genes, namely, IFIT3, XAF1, RSAD2, and MX1, which can be further explored in subsequent studies for their specific molecular mechanisms in HF.https://doi.org/10.1186/s12967-022-03605-2Heart failureMitochondriaCompeting endogenous RNA (ceRNA) networkKey genesBioinformatics |
| spellingShingle | Haozhen Yu Mujun Yu Zhuang Li Enhu Zhang Heng Ma Identification and analysis of mitochondria-related key genes of heart failure Journal of Translational Medicine Heart failure Mitochondria Competing endogenous RNA (ceRNA) network Key genes Bioinformatics |
| title | Identification and analysis of mitochondria-related key genes of heart failure |
| title_full | Identification and analysis of mitochondria-related key genes of heart failure |
| title_fullStr | Identification and analysis of mitochondria-related key genes of heart failure |
| title_full_unstemmed | Identification and analysis of mitochondria-related key genes of heart failure |
| title_short | Identification and analysis of mitochondria-related key genes of heart failure |
| title_sort | identification and analysis of mitochondria related key genes of heart failure |
| topic | Heart failure Mitochondria Competing endogenous RNA (ceRNA) network Key genes Bioinformatics |
| url | https://doi.org/10.1186/s12967-022-03605-2 |
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