In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets
Type 2 diabetes (T2D) is a major global public health burden, with β-cell dysfunction a key component in its pathogenesis. However, the exact pathogenesis of β-cell dysfunction in T2D is yet to be fully elucidated. Ferroptosis, a recently discovered regulated form of non-apoptotic cell death, plays...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.946492/full |
| _version_ | 1811221256633057280 |
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| author | Meiqi Yin Liang Zhou Yanan Ji Rongxin Lu Wei Ji Guorong Jiang Jin Ma Jin Ma Xiudao Song |
| author_facet | Meiqi Yin Liang Zhou Yanan Ji Rongxin Lu Wei Ji Guorong Jiang Jin Ma Jin Ma Xiudao Song |
| author_sort | Meiqi Yin |
| collection | DOAJ |
| description | Type 2 diabetes (T2D) is a major global public health burden, with β-cell dysfunction a key component in its pathogenesis. However, the exact pathogenesis of β-cell dysfunction in T2D is yet to be fully elucidated. Ferroptosis, a recently discovered regulated form of non-apoptotic cell death, plays a vital role in the development of diabetes and its complications. The current study aimed to identify the key molecules involved in β-cell ferroptosis3 in patients with T2D using the mRNA expression profile data of GSE25724 by bioinformatic approaches. The differentially expressed mRNAs (DE-mRNAs) in human islets of patients with T2D were screened using the islet mRNA expression profiling data from the Gene Expression Omnibus and their intersection with ferroptosis genes was then obtained. Ferroptosis-related DE-mRNA functional and pathway enrichment analysis in T2D islet were performed. Using a protein-protein interaction (PPI) network constructed from the STRING database, Cytoscape software identified ferroptosis-related hub genes in the T2D islet with a Degree algorithm. We constructed a miRNA-hub gene network using the miRWalk database. We generated a rat model of T2D to assess the expression of hub genes. A total of 1,316 DE-mRNAs were identified in the islet of patients between T2D and non-T2D (NT2D), including 221 and 1,095 up- and down-regulated genes. Gene set enrichment analysis revealed that the ferroptosis-related gene set was significantly different in islets between T2D and NT2D at an overall level. A total of 33 ferroptosis-related DE-mRNAs were identified, most of which were significantly enriched in pathways including ferroptosis. The established PPI network with ferroptosis-related DE-mRNAs identified five hub genes (JUN, NFE2L2, ATG5, KRAS, and HSPA5), and the area under the ROC curve of these five hub genes was 0.929 in the Logistic regression model. We constructed a regulatory network of hub genes and miRNAs, and the results showed that suggesting that hsa-miR-6855-5p, hsa-miR-9985, and hsa-miR-584-5p could regulate most hub genes. In rat model of T2D, the protein expression levels of JUN and NFE2L2 in pancreatic tissues were upregulated and downregulated, respectively. These results contribute to further elucidation of ferroptosis-related molecular mechanisms in the pathogenesis of β-cell dysfunction of T2D. |
| first_indexed | 2024-04-12T07:56:13Z |
| format | Article |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-12T07:56:13Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-03bf0392430440f09893079da35e75522022-12-22T03:41:29ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-08-011310.3389/fendo.2022.946492946492In silico identification and verification of ferroptosis-related genes in type 2 diabetic isletsMeiqi Yin0Liang Zhou1Yanan Ji2Rongxin Lu3Wei Ji4Guorong Jiang5Jin Ma6Jin Ma7Xiudao Song8Department of Endocrinology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaClinical Pharmaceutical Laboratory of Traditional Chinese Medicine, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, ChinaDivision of Rheumatology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaClinical Pharmaceutical Laboratory of Traditional Chinese Medicine, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Pharmacy, Children’s Hospital of Soochow University, Suzhou, ChinaClinical Pharmaceutical Laboratory of Traditional Chinese Medicine, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaType 2 diabetes (T2D) is a major global public health burden, with β-cell dysfunction a key component in its pathogenesis. However, the exact pathogenesis of β-cell dysfunction in T2D is yet to be fully elucidated. Ferroptosis, a recently discovered regulated form of non-apoptotic cell death, plays a vital role in the development of diabetes and its complications. The current study aimed to identify the key molecules involved in β-cell ferroptosis3 in patients with T2D using the mRNA expression profile data of GSE25724 by bioinformatic approaches. The differentially expressed mRNAs (DE-mRNAs) in human islets of patients with T2D were screened using the islet mRNA expression profiling data from the Gene Expression Omnibus and their intersection with ferroptosis genes was then obtained. Ferroptosis-related DE-mRNA functional and pathway enrichment analysis in T2D islet were performed. Using a protein-protein interaction (PPI) network constructed from the STRING database, Cytoscape software identified ferroptosis-related hub genes in the T2D islet with a Degree algorithm. We constructed a miRNA-hub gene network using the miRWalk database. We generated a rat model of T2D to assess the expression of hub genes. A total of 1,316 DE-mRNAs were identified in the islet of patients between T2D and non-T2D (NT2D), including 221 and 1,095 up- and down-regulated genes. Gene set enrichment analysis revealed that the ferroptosis-related gene set was significantly different in islets between T2D and NT2D at an overall level. A total of 33 ferroptosis-related DE-mRNAs were identified, most of which were significantly enriched in pathways including ferroptosis. The established PPI network with ferroptosis-related DE-mRNAs identified five hub genes (JUN, NFE2L2, ATG5, KRAS, and HSPA5), and the area under the ROC curve of these five hub genes was 0.929 in the Logistic regression model. We constructed a regulatory network of hub genes and miRNAs, and the results showed that suggesting that hsa-miR-6855-5p, hsa-miR-9985, and hsa-miR-584-5p could regulate most hub genes. In rat model of T2D, the protein expression levels of JUN and NFE2L2 in pancreatic tissues were upregulated and downregulated, respectively. These results contribute to further elucidation of ferroptosis-related molecular mechanisms in the pathogenesis of β-cell dysfunction of T2D.https://www.frontiersin.org/articles/10.3389/fendo.2022.946492/fulltype 2 diabetesisletferroptosisbioinformatical analysisdifferential expression geneshub gene |
| spellingShingle | Meiqi Yin Liang Zhou Yanan Ji Rongxin Lu Wei Ji Guorong Jiang Jin Ma Jin Ma Xiudao Song In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets Frontiers in Endocrinology type 2 diabetes islet ferroptosis bioinformatical analysis differential expression genes hub gene |
| title | In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets |
| title_full | In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets |
| title_fullStr | In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets |
| title_full_unstemmed | In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets |
| title_short | In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets |
| title_sort | in silico identification and verification of ferroptosis related genes in type 2 diabetic islets |
| topic | type 2 diabetes islet ferroptosis bioinformatical analysis differential expression genes hub gene |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.946492/full |
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