Differential Expression Profiles of the Transcriptome and miRNA Interactome in Synovial Fibroblasts of Rheumatoid Arthritis Revealed by Next Generation Sequencing
Using next-generation sequencing to decipher the molecular mechanisms underlying aberrant rheumatoid arthritis synovial fibroblasts (RASF) activation, we performed transcriptome-wide RNA-seq and small RNA-seq on synovial fibroblasts from rheumatoid arthritis (RA) subject and normal donor. Differenti...
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| Format: | Article |
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MDPI AG
2019-08-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/9/3/98 |
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| author | Chia-Chun Tseng Ling-Yu Wu Wen-Chan Tsai Tsan-Teng Ou Cheng-Chin Wu Wan-Yu Sung Po-Lin Kuo Jeng-Hsien Yen |
| author_facet | Chia-Chun Tseng Ling-Yu Wu Wen-Chan Tsai Tsan-Teng Ou Cheng-Chin Wu Wan-Yu Sung Po-Lin Kuo Jeng-Hsien Yen |
| author_sort | Chia-Chun Tseng |
| collection | DOAJ |
| description | Using next-generation sequencing to decipher the molecular mechanisms underlying aberrant rheumatoid arthritis synovial fibroblasts (RASF) activation, we performed transcriptome-wide RNA-seq and small RNA-seq on synovial fibroblasts from rheumatoid arthritis (RA) subject and normal donor. Differential expression of mRNA and miRNA was integrated with interaction analysis, functional annotation, regulatory network mapping and experimentally verified miRNA−target interaction data, further validated with microarray expression profiles. In this study, 3049 upregulated mRNA and 3552 downregulated mRNA, together with 50 upregulated miRNA and 35 downregulated miRNA in RASF were identified. Interaction analysis highlighted contribution of miRNA to altered transcriptome. Functional annotation revealed metabolic deregulation and oncogenic signatures of RASF. Regulatory network mapping identified downregulated FOXO1 as master transcription factor resulting in altered transcriptome of RASF. Differential expression in three miRNA and corresponding targets (hsa-miR-31-5p:WASF3, hsa-miR-132-3p:RB1, hsa-miR-29c-3p:COL1A1) were also validated. The interactions of these three miRNA−target genes were experimentally validated with past literature. Our transcriptomic and miRNA interactomic investigation identified gene signatures associated with RASF and revealed the involvement of transcription factors and miRNA in an altered transcriptome. These findings help facilitate our understanding of RA with the hope of serving as a springboard for further discoveries relating to the disease. |
| first_indexed | 2024-04-11T12:42:34Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-04-11T12:42:34Z |
| publishDate | 2019-08-01 |
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| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-dc115a5856ad4a8f94934b0ce33197b12022-12-22T04:23:28ZengMDPI AGDiagnostics2075-44182019-08-01939810.3390/diagnostics9030098diagnostics9030098Differential Expression Profiles of the Transcriptome and miRNA Interactome in Synovial Fibroblasts of Rheumatoid Arthritis Revealed by Next Generation SequencingChia-Chun Tseng0Ling-Yu Wu1Wen-Chan Tsai2Tsan-Teng Ou3Cheng-Chin Wu4Wan-Yu Sung5Po-Lin Kuo6Jeng-Hsien Yen7Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanUsing next-generation sequencing to decipher the molecular mechanisms underlying aberrant rheumatoid arthritis synovial fibroblasts (RASF) activation, we performed transcriptome-wide RNA-seq and small RNA-seq on synovial fibroblasts from rheumatoid arthritis (RA) subject and normal donor. Differential expression of mRNA and miRNA was integrated with interaction analysis, functional annotation, regulatory network mapping and experimentally verified miRNA−target interaction data, further validated with microarray expression profiles. In this study, 3049 upregulated mRNA and 3552 downregulated mRNA, together with 50 upregulated miRNA and 35 downregulated miRNA in RASF were identified. Interaction analysis highlighted contribution of miRNA to altered transcriptome. Functional annotation revealed metabolic deregulation and oncogenic signatures of RASF. Regulatory network mapping identified downregulated FOXO1 as master transcription factor resulting in altered transcriptome of RASF. Differential expression in three miRNA and corresponding targets (hsa-miR-31-5p:WASF3, hsa-miR-132-3p:RB1, hsa-miR-29c-3p:COL1A1) were also validated. The interactions of these three miRNA−target genes were experimentally validated with past literature. Our transcriptomic and miRNA interactomic investigation identified gene signatures associated with RASF and revealed the involvement of transcription factors and miRNA in an altered transcriptome. These findings help facilitate our understanding of RA with the hope of serving as a springboard for further discoveries relating to the disease.https://www.mdpi.com/2075-4418/9/3/98rheumatoid arthritismiRNAsynovial fibroblast |
| spellingShingle | Chia-Chun Tseng Ling-Yu Wu Wen-Chan Tsai Tsan-Teng Ou Cheng-Chin Wu Wan-Yu Sung Po-Lin Kuo Jeng-Hsien Yen Differential Expression Profiles of the Transcriptome and miRNA Interactome in Synovial Fibroblasts of Rheumatoid Arthritis Revealed by Next Generation Sequencing Diagnostics rheumatoid arthritis miRNA synovial fibroblast |
| title | Differential Expression Profiles of the Transcriptome and miRNA Interactome in Synovial Fibroblasts of Rheumatoid Arthritis Revealed by Next Generation Sequencing |
| title_full | Differential Expression Profiles of the Transcriptome and miRNA Interactome in Synovial Fibroblasts of Rheumatoid Arthritis Revealed by Next Generation Sequencing |
| title_fullStr | Differential Expression Profiles of the Transcriptome and miRNA Interactome in Synovial Fibroblasts of Rheumatoid Arthritis Revealed by Next Generation Sequencing |
| title_full_unstemmed | Differential Expression Profiles of the Transcriptome and miRNA Interactome in Synovial Fibroblasts of Rheumatoid Arthritis Revealed by Next Generation Sequencing |
| title_short | Differential Expression Profiles of the Transcriptome and miRNA Interactome in Synovial Fibroblasts of Rheumatoid Arthritis Revealed by Next Generation Sequencing |
| title_sort | differential expression profiles of the transcriptome and mirna interactome in synovial fibroblasts of rheumatoid arthritis revealed by next generation sequencing |
| topic | rheumatoid arthritis miRNA synovial fibroblast |
| url | https://www.mdpi.com/2075-4418/9/3/98 |
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