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Open AccessArticle

Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis

1
Department of Medicine, University of Verona, 37134 Verona, Italy
2
Department of Experimental Medicine—Section of Histology, University of Genova, 16132 Genova, Italy
*
Author to whom correspondence should be addressed.
These authors contributed to this paper equally.
Cells 2019, 8(8), 816; https://doi.org/10.3390/cells8080816
Received: 30 May 2019 / Revised: 16 July 2019 / Accepted: 31 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue The Molecular and Cellular Basis for Rheumatoid Arthritis)
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Abstract

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. View Full-Text
Keywords: long non-coding RNA; microRNA; protein‒protein interaction network; gene module long non-coding RNA; microRNA; protein‒protein interaction network; gene module
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Dolcino, M.; Tinazzi, E.; Puccetti, A.; Lunardi, C. Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis. Cells 2019, 8, 816.

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