Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression
BackgroundDepression is a prevalent mental disorder, which is difficult to diagnose and treat due to its unclear pathogenic mechanisms. The discovery of novel and effective therapeutic targets for depression is urgently needed. The hippocampus is a crucial region involved in depression and has been...
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.589370/full |
| _version_ | 1818561339837120512 |
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| author | Jing Yang Chaoqin Chen Xiaoyuan Jin Lu Liu Jiajia Lin Xianhui Kang Shengmei Zhu |
| author_facet | Jing Yang Chaoqin Chen Xiaoyuan Jin Lu Liu Jiajia Lin Xianhui Kang Shengmei Zhu |
| author_sort | Jing Yang |
| collection | DOAJ |
| description | BackgroundDepression is a prevalent mental disorder, which is difficult to diagnose and treat due to its unclear pathogenic mechanisms. The discovery of novel and effective therapeutic targets for depression is urgently needed. The hippocampus is a crucial region involved in depression and has been a therapeutic target for many antidepressants. Thus, it is beneficial for comprehensive research to be carried out on the molecular mechanisms of the hippocampus involved in the pathogenesis of depression. This study aims to investigate the differentially expressed genes (DEG) in the hippocampus in a chronic unpredictable mild stress (CUMS) mouse model.MethodThe study obtained GSE84183 from the GEO database. The R language screened the differential expression genes (DEG) in the hippocampus tissue of depressed mice, and the enrichment pathways of DEGs were analyzed. A protein-protein interaction (PPI) network was constructed in the STRING database and visualized in Cytoscape software. MicroRNAs for these DEGs were obtained from TarBase and mortar base databases, and transcription factors (TF) related to DEG were predicted from the ENCODE database. Both networks used the visual analysis platform NetworkAnalyst. Finally, the microRNA-TF network was integrated based on the above two networks and imported into Cytoscape for further analysis.ResultsThis study screened 325 differentially expressed genes, containing 42 downregulated genes and 283 upregulated genes. Most of these genes are enriched in the cell cycle and the chemokine signaling pathway. Meanwhile, Wfs1, one of the top ten DEGs, was identified as the key regulator of the cell cycle and the participator in the highest number of modules screened out in PPI networks. Wfs1-related molecules, including UBTF, mmu-mir-17-5p, and mmu-mir-7b-5p, were therefore screened out. Furthermore, we confirmed the downregulation of Wfs1 and upregulation of UBTF/mmu-mir-17-5p/mmu-mir-7b-5p in the hippocampus of the CUMS mouse model. Our data indicate that Wfs1 and related molecules were predicted to be associated with the pathological process of depression. This research provided potential new molecular targets of stress-induced depression. |
| first_indexed | 2024-12-14T00:49:34Z |
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| id | doaj.art-72e7d6b65d0f4b36a647fe4778e8cb59 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-14T00:49:34Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-72e7d6b65d0f4b36a647fe4778e8cb592022-12-21T23:23:56ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-01-011110.3389/fgene.2020.589370589370Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of DepressionJing Yang0Chaoqin Chen1Xiaoyuan Jin2Lu Liu3Jiajia Lin4Xianhui Kang5Shengmei Zhu6Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Public Health, University of Minnesota Twin Cities, Minneapolis, MN, United StatesDepartment of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Neurobiology, The Innovation Center for Brain Science, Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaBackgroundDepression is a prevalent mental disorder, which is difficult to diagnose and treat due to its unclear pathogenic mechanisms. The discovery of novel and effective therapeutic targets for depression is urgently needed. The hippocampus is a crucial region involved in depression and has been a therapeutic target for many antidepressants. Thus, it is beneficial for comprehensive research to be carried out on the molecular mechanisms of the hippocampus involved in the pathogenesis of depression. This study aims to investigate the differentially expressed genes (DEG) in the hippocampus in a chronic unpredictable mild stress (CUMS) mouse model.MethodThe study obtained GSE84183 from the GEO database. The R language screened the differential expression genes (DEG) in the hippocampus tissue of depressed mice, and the enrichment pathways of DEGs were analyzed. A protein-protein interaction (PPI) network was constructed in the STRING database and visualized in Cytoscape software. MicroRNAs for these DEGs were obtained from TarBase and mortar base databases, and transcription factors (TF) related to DEG were predicted from the ENCODE database. Both networks used the visual analysis platform NetworkAnalyst. Finally, the microRNA-TF network was integrated based on the above two networks and imported into Cytoscape for further analysis.ResultsThis study screened 325 differentially expressed genes, containing 42 downregulated genes and 283 upregulated genes. Most of these genes are enriched in the cell cycle and the chemokine signaling pathway. Meanwhile, Wfs1, one of the top ten DEGs, was identified as the key regulator of the cell cycle and the participator in the highest number of modules screened out in PPI networks. Wfs1-related molecules, including UBTF, mmu-mir-17-5p, and mmu-mir-7b-5p, were therefore screened out. Furthermore, we confirmed the downregulation of Wfs1 and upregulation of UBTF/mmu-mir-17-5p/mmu-mir-7b-5p in the hippocampus of the CUMS mouse model. Our data indicate that Wfs1 and related molecules were predicted to be associated with the pathological process of depression. This research provided potential new molecular targets of stress-induced depression.https://www.frontiersin.org/articles/10.3389/fgene.2020.589370/fulldepressionHippcampusWfs1CUMSmicroRNAs |
| spellingShingle | Jing Yang Chaoqin Chen Xiaoyuan Jin Lu Liu Jiajia Lin Xianhui Kang Shengmei Zhu Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression Frontiers in Genetics depression Hippcampus Wfs1 CUMS microRNAs |
| title | Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression |
| title_full | Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression |
| title_fullStr | Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression |
| title_full_unstemmed | Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression |
| title_short | Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression |
| title_sort | wfs1 and related molecules as key candidate genes in the hippocampus of depression |
| topic | depression Hippcampus Wfs1 CUMS microRNAs |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2020.589370/full |
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