Bioinformatics-Based Identification of MicroRNA-Regulated and Rheumatoid Arthritis-Associated Genes.

Yi-Jiang Song,Jian-Hua He,Guiling Li,Yao Guo,Li Yang,Yi Xing

doi:10.1371/journal.pone.0137551

Yi-Jiang Song, Jian-Hua He + Show 4 more

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https://doi.org/10.1371/journal.pone.0137551

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Journal: PloS one	Publication Date: Sep 11, 2015
Citations: 23	License type: CC BY 4.0

Affiliation: Chongqing University, Wenzhou Medical University

Abstract

MicroRNAs (miRNAs) act as epigenetic markers and regulate the expression of their target genes, including those characterized as regulators in autoimmune diseases. Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. The potential roles of miRNA-regulated genes in RA pathogenesis have greatly aroused the interest of clinicians and researchers in recent years. In the current study, RA-related miRNAs records were obtained from PubMed through conditional literature retrieval. After analyzing the selected records, miRNA targeted genes were predicted. We identified 14 RA-associated miRNAs, and their sub-analysis in 5 microarray or RNA sequencing (RNA-seq) datasets was performed. The microarray and RNA-seq data of RA were also downloaded from NCBI Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA), analyzed, and annotated. Using a bioinformatics approach, we identified a series of differentially expressed genes (DEGs) by comparing studies on RA and the controls. The RA-related gene expression profile was thus obtained and the expression of miRNA-regulated genes was analyzed. After functional annotation analysis, we found GO molecular function (MF) terms significantly enriched in calcium ion binding (GO: 0005509). Moreover, some novel dysregulated target genes were identified in RA through integrated analysis of miRNA/mRNA expression. The result revealed that the expression of a number of genes, including ROR2, ABI3BP, SMOC2, etc., was not only affected by dysregulated miRNAs, but also altered in RA. Our findings indicate that there is a close association between negatively correlated mRNA/miRNA pairs and RA. These findings may be applied to identify genetic markers for RA diagnosis and treatment in the future.

Highlights

Rheumatoid arthritis (RA) is a highly prevalent chronic immune-mediated inflammatory disease, principally leading to injury of the synovial joint, as well as affecting many other tissues [1, 2]
Synovial fibroblasts (SFs), known as fibroblast-like synoviocytes, are a special cell type located inside joints in the synovium, and they play a crucial role in the pathogenesis of rheumatoid arthritis (RA) [6, 7]
Our results showed that the Gene Ontology (GO) molecular function (MF) terms of both microarray and sequencing data were enriched in calcium ion binding (GO: 0005509) and carbohydrate binding (GO: 0030246)

Summary

Introduction

Rheumatoid arthritis (RA) is a highly prevalent chronic immune-mediated inflammatory disease, principally leading to injury of the synovial joint, as well as affecting many other tissues [1, 2]. In the developed world approximately 0.5%-1% of adults suffer from joint and other bone pains during their lifetime, leading to chronic disability or even death. Synovial fibroblasts (SFs), known as fibroblast-like synoviocytes, are a special cell type located inside joints in the synovium, and they play a crucial role in the pathogenesis of RA [6, 7]. RA is characterized by increased levels of SF-secreted proinflammatory cytokines that promote extracellular matrix degradation, chemokine production, and progressive destruction of joint membrane, cartilage and bone [8]. RA-associated SFs (RASFs) secrete growth factors to avoid apoptotic cell death, and they promote angiogenesis [9]. OA patients are often chosen as controls in RA studies [10]

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