Comprehensive Analyses of Type 1 Diabetes Ketosis- or Ketoacidosis-Related Genes in Activated CD56+CD16+ NK Cells
ObjectivesAlterations in natural killer (NK) cells activity cause damage to pancreatic islets in type 1 diabetes mellitus (T1DM). The aim of this study is to identify T1DM ketosis- or ketoacidosis-related genes in activated CD56+CD16+ NK cells.MethodsMicroarray datasets were downloaded from the Gene...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-11-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.750135/full |
| _version_ | 1818743872799375360 |
|---|---|
| author | Ruifeng Shi Fang Dai Yong He Li Sun Min Xu Datong Deng Qiu Zhang |
| author_facet | Ruifeng Shi Fang Dai Yong He Li Sun Min Xu Datong Deng Qiu Zhang |
| author_sort | Ruifeng Shi |
| collection | DOAJ |
| description | ObjectivesAlterations in natural killer (NK) cells activity cause damage to pancreatic islets in type 1 diabetes mellitus (T1DM). The aim of this study is to identify T1DM ketosis- or ketoacidosis-related genes in activated CD56+CD16+ NK cells.MethodsMicroarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using the GEO2R tool. Enrichment analyses were performed using Metascape online database and GSEA software. Cell-specific gene co-expression network was built using NetworkAnalyst tools. Cytoscape software was used to identify hub genes and construct co-expressed networks. Target miRNAs were predicted based on the DIANA-micro T, miRDB, and miRWalk online databases.ResultsA total of 70 DEGs were identified between T1DM patients recovered from ketosis or ketoacidosis and healthy control blood samples in GSE44314. Among the DEGs, 10 hub genes were screened out. The mature NK cell-specific gene co-expression network for DEGs in T1DM was built using NetworkAnalyst tools. DEGs between activated CD56+CD16+ NK cells and CD56brightCD16- NK cells were identified from GSE1511. After intersection, 13 overlapping genes between GSE44314 and GSE1511 microarray datasets were screened out, in which 7 hub genes were identified. Additionally, 59 target miRNAs were predicted according to the 7 hub genes. After validating with the exosome miRNA expression profile dataset of GSE97123, seven differentially expressed miRNAs (DEmiRNAs) in plasma-derived exosome were selected. Finally, a mRNA–miRNA network was constructed, which was involved in the T1DM ketosis or ketoacidosis process.ConclusionThis work identified seven hub genes in activated CD56+CD16+ NK cells and seven miRNAs in plasma-derived exosome as potential predictors of T1DM ketoacidosis, which provided a novel insight for the pathogenesis at the transcriptome level. |
| first_indexed | 2024-12-18T02:35:19Z |
| format | Article |
| id | doaj.art-3b9eefd5f9704e16a6698af69a40f7bb |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-18T02:35:19Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-3b9eefd5f9704e16a6698af69a40f7bb2022-12-21T21:23:48ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-11-011210.3389/fendo.2021.750135750135Comprehensive Analyses of Type 1 Diabetes Ketosis- or Ketoacidosis-Related Genes in Activated CD56+CD16+ NK CellsRuifeng ShiFang DaiYong HeLi SunMin XuDatong DengQiu ZhangObjectivesAlterations in natural killer (NK) cells activity cause damage to pancreatic islets in type 1 diabetes mellitus (T1DM). The aim of this study is to identify T1DM ketosis- or ketoacidosis-related genes in activated CD56+CD16+ NK cells.MethodsMicroarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using the GEO2R tool. Enrichment analyses were performed using Metascape online database and GSEA software. Cell-specific gene co-expression network was built using NetworkAnalyst tools. Cytoscape software was used to identify hub genes and construct co-expressed networks. Target miRNAs were predicted based on the DIANA-micro T, miRDB, and miRWalk online databases.ResultsA total of 70 DEGs were identified between T1DM patients recovered from ketosis or ketoacidosis and healthy control blood samples in GSE44314. Among the DEGs, 10 hub genes were screened out. The mature NK cell-specific gene co-expression network for DEGs in T1DM was built using NetworkAnalyst tools. DEGs between activated CD56+CD16+ NK cells and CD56brightCD16- NK cells were identified from GSE1511. After intersection, 13 overlapping genes between GSE44314 and GSE1511 microarray datasets were screened out, in which 7 hub genes were identified. Additionally, 59 target miRNAs were predicted according to the 7 hub genes. After validating with the exosome miRNA expression profile dataset of GSE97123, seven differentially expressed miRNAs (DEmiRNAs) in plasma-derived exosome were selected. Finally, a mRNA–miRNA network was constructed, which was involved in the T1DM ketosis or ketoacidosis process.ConclusionThis work identified seven hub genes in activated CD56+CD16+ NK cells and seven miRNAs in plasma-derived exosome as potential predictors of T1DM ketoacidosis, which provided a novel insight for the pathogenesis at the transcriptome level.https://www.frontiersin.org/articles/10.3389/fendo.2021.750135/fulltype 1 diabetes mellitusketosisketoacidosisNK cells subsetdifferentially expressed genes |
| spellingShingle | Ruifeng Shi Fang Dai Yong He Li Sun Min Xu Datong Deng Qiu Zhang Comprehensive Analyses of Type 1 Diabetes Ketosis- or Ketoacidosis-Related Genes in Activated CD56+CD16+ NK Cells Frontiers in Endocrinology type 1 diabetes mellitus ketosis ketoacidosis NK cells subset differentially expressed genes |
| title | Comprehensive Analyses of Type 1 Diabetes Ketosis- or Ketoacidosis-Related Genes in Activated CD56+CD16+ NK Cells |
| title_full | Comprehensive Analyses of Type 1 Diabetes Ketosis- or Ketoacidosis-Related Genes in Activated CD56+CD16+ NK Cells |
| title_fullStr | Comprehensive Analyses of Type 1 Diabetes Ketosis- or Ketoacidosis-Related Genes in Activated CD56+CD16+ NK Cells |
| title_full_unstemmed | Comprehensive Analyses of Type 1 Diabetes Ketosis- or Ketoacidosis-Related Genes in Activated CD56+CD16+ NK Cells |
| title_short | Comprehensive Analyses of Type 1 Diabetes Ketosis- or Ketoacidosis-Related Genes in Activated CD56+CD16+ NK Cells |
| title_sort | comprehensive analyses of type 1 diabetes ketosis or ketoacidosis related genes in activated cd56 cd16 nk cells |
| topic | type 1 diabetes mellitus ketosis ketoacidosis NK cells subset differentially expressed genes |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.750135/full |
| work_keys_str_mv | AT ruifengshi comprehensiveanalysesoftype1diabetesketosisorketoacidosisrelatedgenesinactivatedcd56cd16nkcells AT fangdai comprehensiveanalysesoftype1diabetesketosisorketoacidosisrelatedgenesinactivatedcd56cd16nkcells AT yonghe comprehensiveanalysesoftype1diabetesketosisorketoacidosisrelatedgenesinactivatedcd56cd16nkcells AT lisun comprehensiveanalysesoftype1diabetesketosisorketoacidosisrelatedgenesinactivatedcd56cd16nkcells AT minxu comprehensiveanalysesoftype1diabetesketosisorketoacidosisrelatedgenesinactivatedcd56cd16nkcells AT datongdeng comprehensiveanalysesoftype1diabetesketosisorketoacidosisrelatedgenesinactivatedcd56cd16nkcells AT qiuzhang comprehensiveanalysesoftype1diabetesketosisorketoacidosisrelatedgenesinactivatedcd56cd16nkcells |