Bioinformatics-Based Identification of MicroRNA-Regulated and Rheumatoid Arthritis-Associated Genes.
Bioinformatics-Based Identification of MicroRNA-Regulated and Rheumatoid Arthritis-Associated Genes.
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基于生物信息学的 MicroRNA 调节和类风湿关节炎相关基因的鉴定
DOI：
10.1371/journal.pone.0137551
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Song YJ;Li G;He JH;Guo Y;Yang L
microRNA（miRNAs）作为表观遗传标记物并调节其靶基因的表达，包括那些在自身免疫性疾病中被表征为调节剂的基因。类风湿性关节炎（RA）是最常见的自身免疫性疾病之一。近年来，miRNA调控基因在类风湿关节炎发病机制中的作用引起了临床医生和研究人员的极大兴趣。本研究通过条件性文献检索从PubMed获得RA相关miRNAs记录。在分析所选择的记录之后，预测miRNA靶向基因。我们鉴定了14种RA相关的miRNA，并在5个微阵列或RNA测序（RNA-seq）数据集中进行了亚分析。RA的微阵列和RNA-seq数据也从NCBI基因表达综合库（GEO）和序列读取档案（SRA）下载，分析并注释。利用生物信息学的方法，我们确定了一系列的差异表达基因（DEG），通过比较研究RA和对照组。由此获得RA相关基因表达谱，并分析miRNA调控基因的表达。在功能注释分析后，我们发现GO分子功能（MF）项显著富集在钙离子结合（GO：0005509）。此外，通过对miRNA/mRNA表达的综合分析，在RA中发现了一些新的失调靶基因。结果表明，ROR 2、ABI 3BP、SMOC 2等基因的表达与细胞凋亡密切相关，不仅受到失调的miRNAs的影响，而且在RA中也发生了改变。我们的研究结果表明，有负相关的mRNA/miRNA对和RA之间的密切联系。这些发现可能适用于确定遗传标记，为RA的诊断和治疗在未来。
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.