Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis
Abstract Background Sepsis is a high mortality disease which seriously threatens human life and health, for which the pathogenetic mechanism still unclear. There is increasing evidence showed that immune and inflammation responses are key players in the development of sepsis pathology. LncRNAs, whic...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12864-023-09535-7 |
| _version_ | 1797577966298857472 |
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| author | Tianfeng Wang Si Xu Lei Zhang Tianjun Yang Xiaoqin Fan Chunyan Zhu Yinzhong Wang Fei Tong Qing Mei Aijun Pan |
| author_facet | Tianfeng Wang Si Xu Lei Zhang Tianjun Yang Xiaoqin Fan Chunyan Zhu Yinzhong Wang Fei Tong Qing Mei Aijun Pan |
| author_sort | Tianfeng Wang |
| collection | DOAJ |
| description | Abstract Background Sepsis is a high mortality disease which seriously threatens human life and health, for which the pathogenetic mechanism still unclear. There is increasing evidence showed that immune and inflammation responses are key players in the development of sepsis pathology. LncRNAs, which act as ceRNAs, have critical roles in various diseases. However, the regulatory roles of ceRNA in the immunopathogenesis of sepsis have not yet been elucidated. Results In this study, we aimed to identify immune biomarkers associated with sepsis. We first generated a global immune-associated ceRNA (IMCE) network based on data describing interactions pairs of gene–miRNA and miRNA–lncRNA. Afterward, we excavated a dysregulated sepsis immune-associated ceRNA (SPIMC) network from the global IMCE network by means of a multi-step computational approach. Functional enrichment indicated that lncRNAs in SPIMC network have pivotal roles in the immune mechanism underlying sepsis. Subsequently, we identified module and hub genes (CD4 and STAT4) via construction of a sepsis immune-related PPI network. Then, we identified hub genes based on the modular structure of PPI network and generated a ceRNA subnetwork to analyze key lncRNAs associated with sepsis. Finally, 6 lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) that identified as immune biomarkers of sepsis. Moreover, the CIBERSORT algorithm and the infiltration of circulating immune cells types were performed to identify the inflammatory state of sepsis. Correlation analyses between immune cells and sepsis immune biomarkers showed that the LINC00265 was strongly positive correlated with the macrophages M2 (r = 0.77). Conclusion Collectively, these results may suggest that these lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) played important roles in the immune pathogenesis of sepsis and provide potential therapeutic targets for further researches on immune therapy treatment in patients with sepsis. |
| first_indexed | 2024-03-10T22:15:35Z |
| format | Article |
| id | doaj.art-9d5ce0c4c1c048e98795f9b343d3ef06 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-03-10T22:15:35Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-9d5ce0c4c1c048e98795f9b343d3ef062023-11-19T12:27:59ZengBMCBMC Genomics1471-21642023-08-0124111510.1186/s12864-023-09535-7Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysisTianfeng Wang0Si Xu1Lei Zhang2Tianjun Yang3Xiaoqin Fan4Chunyan Zhu5Yinzhong Wang6Fei Tong7Qing Mei8Aijun Pan9Department of Critical Care Medicine, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of ChinaDepartment of Neurology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Critical Care Medicine, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of ChinaDepartment of Critical Care Medicine, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of ChinaDepartment of Critical Care Medicine, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of ChinaDepartment of Critical Care Medicine, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of ChinaDepartment of Critical Care Medicine, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of ChinaDepartment of Critical Care Medicine, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of ChinaDepartment of Critical Care Medicine, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of ChinaDepartment of Critical Care Medicine, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of ChinaAbstract Background Sepsis is a high mortality disease which seriously threatens human life and health, for which the pathogenetic mechanism still unclear. There is increasing evidence showed that immune and inflammation responses are key players in the development of sepsis pathology. LncRNAs, which act as ceRNAs, have critical roles in various diseases. However, the regulatory roles of ceRNA in the immunopathogenesis of sepsis have not yet been elucidated. Results In this study, we aimed to identify immune biomarkers associated with sepsis. We first generated a global immune-associated ceRNA (IMCE) network based on data describing interactions pairs of gene–miRNA and miRNA–lncRNA. Afterward, we excavated a dysregulated sepsis immune-associated ceRNA (SPIMC) network from the global IMCE network by means of a multi-step computational approach. Functional enrichment indicated that lncRNAs in SPIMC network have pivotal roles in the immune mechanism underlying sepsis. Subsequently, we identified module and hub genes (CD4 and STAT4) via construction of a sepsis immune-related PPI network. Then, we identified hub genes based on the modular structure of PPI network and generated a ceRNA subnetwork to analyze key lncRNAs associated with sepsis. Finally, 6 lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) that identified as immune biomarkers of sepsis. Moreover, the CIBERSORT algorithm and the infiltration of circulating immune cells types were performed to identify the inflammatory state of sepsis. Correlation analyses between immune cells and sepsis immune biomarkers showed that the LINC00265 was strongly positive correlated with the macrophages M2 (r = 0.77). Conclusion Collectively, these results may suggest that these lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) played important roles in the immune pathogenesis of sepsis and provide potential therapeutic targets for further researches on immune therapy treatment in patients with sepsis.https://doi.org/10.1186/s12864-023-09535-7SepsisImmune-related geneslncRNABiomarkerNetwork analysis |
| spellingShingle | Tianfeng Wang Si Xu Lei Zhang Tianjun Yang Xiaoqin Fan Chunyan Zhu Yinzhong Wang Fei Tong Qing Mei Aijun Pan Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis BMC Genomics Sepsis Immune-related genes lncRNA Biomarker Network analysis |
| title | Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis |
| title_full | Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis |
| title_fullStr | Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis |
| title_full_unstemmed | Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis |
| title_short | Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis |
| title_sort | identification of immune related lncrna in sepsis by construction of cerna network and integrating bioinformatic analysis |
| topic | Sepsis Immune-related genes lncRNA Biomarker Network analysis |
| url | https://doi.org/10.1186/s12864-023-09535-7 |
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