Identification of Key Genes and Pathways in RBCK1 Deficient patients by Gene Expression Profiling
HOIL-1/RBCK1 deficiency is a new autosomal receive disorder with unstable cellular responses to pro-inflammatory cytokines, resulting in auto-inflammation, pyogenic bacterial disease, as well as the development of muscular amylopectinosis. This study explored the molecular mechanisms of RBCK1 defici...
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| Format: | Article |
| Language: | English |
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Tehran University of Medical Sciences
2021-07-01
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| Series: | Acta Medica Iranica |
| Subjects: | |
| Online Access: | https://acta.tums.ac.ir/index.php/acta/article/view/8589 |
| _version_ | 1828140110468612096 |
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| author | Khyber Shinwari Mikhail A. Bolkov Irina A. Tuzankina Valery A. Chereshnev |
| author_facet | Khyber Shinwari Mikhail A. Bolkov Irina A. Tuzankina Valery A. Chereshnev |
| author_sort | Khyber Shinwari |
| collection | DOAJ |
| description | HOIL-1/RBCK1 deficiency is a new autosomal receive disorder with unstable cellular responses to pro-inflammatory cytokines, resulting in auto-inflammation, pyogenic bacterial disease, as well as the development of muscular amylopectinosis. This study explored the molecular mechanisms of RBCK1 deficiency with integrated bioinformatics analyses of the feature genes and the correlative gene functions. The expression profile of GSE24519 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between RBCK1, MYDK88, NEMO deficient fibroblast, and healthy fibroblast specimens were identified. Gene ontology (GO) enrichment analysis on gene functions and the Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed by using Database for Annotation, Visualization, and Integrated Discovery (DAVID). Cytoscape was used to visualize the protein-protein interaction (PPI) of these DEGs. GO analysis revealed that the “Skeletal system development, Extracellular matrix organization, Positive regulation of cell migration, Negative regulation of canonical Wnt signaling pathway, Cell adhesion, Angiogenesis and Negative regulation of BMP signaling pathway, Serine-type carboxypeptidase activity, Polysaccharide binding, Calcium ion binding, frizzled binding, Neuropilin binding, and cell adhesion molecule binding, extracellular exosome, extracellular space, extracellular region, lysosomal lumen, endoplasmic reticulum lumen, cell surface and focal adhesion to BP, MF, and CC, respectively. The KEGG pathway analysis showed that the complement and coagulation cascade, ECM receptor interactions, PI3K- Akt signaling pathway, PPAR signaling pathway, TGF-beta signaling pathway, Pathway in Cancer, Viral carcinogenesis and Focal adhesion pathway were closely associated with RBCK1 deficiency occurrence. Importantly, TK1, AURKB, CDCA2, UBE2C, KIFC1, CEP55, CDCA3, GINS2, MCM6, and CDC45 were predicted to be significantly related to RCBK1 deficiency. Our discovery provides a registry of genes and pathways that are disrupted in RCBK1, which will enhance in understanding the pathogenesis of RBCK1 deficiency and other innate immunodeficiency diseases. This study has the potential to be used in the clinic for diagnosis and targeted therapy of RCBKI and other innate immunodeficiencies in the future. |
| first_indexed | 2024-04-11T19:03:06Z |
| format | Article |
| id | doaj.art-9e45b29825104fce85736eec572ef12b |
| institution | Directory Open Access Journal |
| issn | 0044-6025 1735-9694 |
| language | English |
| last_indexed | 2024-04-11T19:03:06Z |
| publishDate | 2021-07-01 |
| publisher | Tehran University of Medical Sciences |
| record_format | Article |
| series | Acta Medica Iranica |
| spelling | doaj.art-9e45b29825104fce85736eec572ef12b2022-12-22T04:07:53ZengTehran University of Medical SciencesActa Medica Iranica0044-60251735-96942021-07-0159510.18502/acta.v59i5.6661Identification of Key Genes and Pathways in RBCK1 Deficient patients by Gene Expression ProfilingKhyber Shinwari0Mikhail A. Bolkov1Irina A. Tuzankina2Valery A. Chereshnev3Ural Federal UniversityInstitute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia.Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia.Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia.HOIL-1/RBCK1 deficiency is a new autosomal receive disorder with unstable cellular responses to pro-inflammatory cytokines, resulting in auto-inflammation, pyogenic bacterial disease, as well as the development of muscular amylopectinosis. This study explored the molecular mechanisms of RBCK1 deficiency with integrated bioinformatics analyses of the feature genes and the correlative gene functions. The expression profile of GSE24519 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between RBCK1, MYDK88, NEMO deficient fibroblast, and healthy fibroblast specimens were identified. Gene ontology (GO) enrichment analysis on gene functions and the Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed by using Database for Annotation, Visualization, and Integrated Discovery (DAVID). Cytoscape was used to visualize the protein-protein interaction (PPI) of these DEGs. GO analysis revealed that the “Skeletal system development, Extracellular matrix organization, Positive regulation of cell migration, Negative regulation of canonical Wnt signaling pathway, Cell adhesion, Angiogenesis and Negative regulation of BMP signaling pathway, Serine-type carboxypeptidase activity, Polysaccharide binding, Calcium ion binding, frizzled binding, Neuropilin binding, and cell adhesion molecule binding, extracellular exosome, extracellular space, extracellular region, lysosomal lumen, endoplasmic reticulum lumen, cell surface and focal adhesion to BP, MF, and CC, respectively. The KEGG pathway analysis showed that the complement and coagulation cascade, ECM receptor interactions, PI3K- Akt signaling pathway, PPAR signaling pathway, TGF-beta signaling pathway, Pathway in Cancer, Viral carcinogenesis and Focal adhesion pathway were closely associated with RBCK1 deficiency occurrence. Importantly, TK1, AURKB, CDCA2, UBE2C, KIFC1, CEP55, CDCA3, GINS2, MCM6, and CDC45 were predicted to be significantly related to RCBK1 deficiency. Our discovery provides a registry of genes and pathways that are disrupted in RCBK1, which will enhance in understanding the pathogenesis of RBCK1 deficiency and other innate immunodeficiency diseases. This study has the potential to be used in the clinic for diagnosis and targeted therapy of RCBKI and other innate immunodeficiencies in the future.https://acta.tums.ac.ir/index.php/acta/article/view/8589Primary immunodeficiencyRBCK1 deficiencyDifferential expressed genesKey pathwaysHub genesMicroarray |
| spellingShingle | Khyber Shinwari Mikhail A. Bolkov Irina A. Tuzankina Valery A. Chereshnev Identification of Key Genes and Pathways in RBCK1 Deficient patients by Gene Expression Profiling Acta Medica Iranica Primary immunodeficiency RBCK1 deficiency Differential expressed genes Key pathways Hub genes Microarray |
| title | Identification of Key Genes and Pathways in RBCK1 Deficient patients by Gene Expression Profiling |
| title_full | Identification of Key Genes and Pathways in RBCK1 Deficient patients by Gene Expression Profiling |
| title_fullStr | Identification of Key Genes and Pathways in RBCK1 Deficient patients by Gene Expression Profiling |
| title_full_unstemmed | Identification of Key Genes and Pathways in RBCK1 Deficient patients by Gene Expression Profiling |
| title_short | Identification of Key Genes and Pathways in RBCK1 Deficient patients by Gene Expression Profiling |
| title_sort | identification of key genes and pathways in rbck1 deficient patients by gene expression profiling |
| topic | Primary immunodeficiency RBCK1 deficiency Differential expressed genes Key pathways Hub genes Microarray |
| url | https://acta.tums.ac.ir/index.php/acta/article/view/8589 |
| work_keys_str_mv | AT khybershinwari identificationofkeygenesandpathwaysinrbck1deficientpatientsbygeneexpressionprofiling AT mikhailabolkov identificationofkeygenesandpathwaysinrbck1deficientpatientsbygeneexpressionprofiling AT irinaatuzankina identificationofkeygenesandpathwaysinrbck1deficientpatientsbygeneexpressionprofiling AT valeryachereshnev identificationofkeygenesandpathwaysinrbck1deficientpatientsbygeneexpressionprofiling |