Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease driven by genetic, environmental and epigenetic factors. Long non-coding RNAs (LncRNAs) are a key component of the epigenetic mechanisms and are known to be involved in the development of autoimmune diseases. In this work we aime...
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MDPI AG
2019-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/8/816 |
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| author | Marzia Dolcino Elisa Tinazzi Antonio Puccetti Claudio Lunardi |
| author_facet | Marzia Dolcino Elisa Tinazzi Antonio Puccetti Claudio Lunardi |
| author_sort | Marzia Dolcino |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease driven by genetic, environmental and epigenetic factors. Long non-coding RNAs (LncRNAs) are a key component of the epigenetic mechanisms and are known to be involved in the development of autoimmune diseases. In this work we aimed to identify significantly differentially expressed LncRNAs (DE-LncRNAs) that are functionally connected to modulated genes strictly associated with RA. In total, 542,500 transcripts have been profiled in peripheral blood mononuclear cells (PBMCs) from four patients with early onset RA prior any treatment and four healthy donors using Clariom D arrays. Results were confirmed by real-time PCR in 20 patients and 20 controls. Six DE-LncRNAs target experimentally validated miRNAs able to regulate differentially expressed genes (DEGs) in RA; among them, only FTX, HNRNPU-AS1 and RP11-498C9.15 targeted a large number of DEGs. Most importantly, RP11-498C9.15 targeted the largest number of signalling pathways that were found to be enriched by the global amount of RA-DEGs and that have already been associated with RA and RA−synoviocytes. Moreover, RP11-498C9.15 targeted the most highly connected genes in the RA interactome, thus suggesting its involvement in crucial gene regulation. These results indicate that, by modulating both microRNAs and gene expression, RP11-498C9.15 may play a pivotal role in RA pathogenesis. |
| first_indexed | 2024-03-12T11:14:16Z |
| format | Article |
| id | doaj.art-0a3c60cfdb7b472cbb8ec6f6af657bbd |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T11:14:16Z |
| publishDate | 2019-08-01 |
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| spelling | doaj.art-0a3c60cfdb7b472cbb8ec6f6af657bbd2023-09-02T02:19:14ZengMDPI AGCells2073-44092019-08-018881610.3390/cells8080816cells8080816Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid ArthritisMarzia Dolcino0Elisa Tinazzi1Antonio Puccetti2Claudio Lunardi3Department of Medicine, University of Verona, 37134 Verona, ItalyDepartment of Medicine, University of Verona, 37134 Verona, ItalyDepartment of Experimental Medicine—Section of Histology, University of Genova, 16132 Genova, ItalyDepartment of Medicine, University of Verona, 37134 Verona, ItalyRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease driven by genetic, environmental and epigenetic factors. Long non-coding RNAs (LncRNAs) are a key component of the epigenetic mechanisms and are known to be involved in the development of autoimmune diseases. In this work we aimed to identify significantly differentially expressed LncRNAs (DE-LncRNAs) that are functionally connected to modulated genes strictly associated with RA. In total, 542,500 transcripts have been profiled in peripheral blood mononuclear cells (PBMCs) from four patients with early onset RA prior any treatment and four healthy donors using Clariom D arrays. Results were confirmed by real-time PCR in 20 patients and 20 controls. Six DE-LncRNAs target experimentally validated miRNAs able to regulate differentially expressed genes (DEGs) in RA; among them, only FTX, HNRNPU-AS1 and RP11-498C9.15 targeted a large number of DEGs. Most importantly, RP11-498C9.15 targeted the largest number of signalling pathways that were found to be enriched by the global amount of RA-DEGs and that have already been associated with RA and RA−synoviocytes. Moreover, RP11-498C9.15 targeted the most highly connected genes in the RA interactome, thus suggesting its involvement in crucial gene regulation. These results indicate that, by modulating both microRNAs and gene expression, RP11-498C9.15 may play a pivotal role in RA pathogenesis.https://www.mdpi.com/2073-4409/8/8/816long non-coding RNAmicroRNAprotein‒protein interaction networkgene module |
| spellingShingle | Marzia Dolcino Elisa Tinazzi Antonio Puccetti Claudio Lunardi Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis Cells long non-coding RNA microRNA protein‒protein interaction network gene module |
| title | Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis |
| title_full | Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis |
| title_fullStr | Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis |
| title_full_unstemmed | Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis |
| title_short | Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis |
| title_sort | long non coding rnas target pathogenetically relevant genes and pathways in rheumatoid arthritis |
| topic | long non-coding RNA microRNA protein‒protein interaction network gene module |
| url | https://www.mdpi.com/2073-4409/8/8/816 |
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