J Rheum Dis.  2011 Dec;18(4):253-263. 10.4078/jrd.2011.18.4.253.

Integrated Analysis of MicroRNA and mRNA Expression Profiles in Rheumatoid Arthritis Synovial Monocytes

• Ji JD
• Kim TH
• Lee B
• Na KS
• Choi SJ
• Lee YH
• Song GG

• KMID: 2223128
• DOI: http://doi.org/10.4078/jrd.2011.18.4.253

Abstract

OBJECTIVE
MicroRNAs (miRNAs) play important roles in many biological processes and recent studies have provided growing evidences that miRNA dysregulation might play important roles in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate the contribution of miRNAs to altered gene expressions in RA.
METHODS
To investigate whether the differential expression of miRNA in RA could account for the altered expression of certain genes, we compared the different expressions of miRNAs and mRNAs in rheumatoid synovial fluid monocytes with that of normal peripheral blood (PB) monocytes by using a gene expression oligonucleotide microarray and a microRNA microarray.
RESULTS
Comparative analysis of the mRNA profiles showed significant different expressions of 430 genes in RA synovial monocytes, of which 303 (70%) were upregulated and 127 (30%) were downregulated, as compared with that of normal PB monocytes. Out of differentially expressed 13 miRNAs, 9 miRNAs were upregulated and 4 miRNAs were downregulated in the RA synovial monocytes. A total of 62 genes were predicted as target genes of the 13 differentially expressed miRNAs in the RA synovial monocytes. Among the 62 miRNA-targeted genes, a few genes such as GSTM1, VIPR1, PADI4, CDA, IL21R, CCL5, IL7R, STAT4, HTRA1 and IL18BP have been reported to be associated with RA.
CONCLUSION
In the present study, we observed that several miRNAs are differentially expressed in RA synovial monocytes, and we suggest that these different expressions of miRNAs may regulate the expression of several genes associated with the pathogenesis of RA.

Keyword

MicroRNA; Rheumatoid arthritis; Microarray

MeSH Terms

Arthritis, Rheumatoid
Biological Processes
Gene Expression
Genes, vif
MicroRNAs
Monocytes
Oligonucleotide Array Sequence Analysis
Receptors, Interleukin-21
RNA, Messenger
Synovial Fluid
MicroRNAs
RNA, Messenger
Receptors, Interleukin-21

Figure

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  Figure 1. Hierarchical clustering of microRNA expression profile between RA synovial monocytes (RA1-RA6) and normal PB monocytes.

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  Figure 2. Validation of the differentially expressed genes and miRNAs in the RA synovial monocytes. The array data for mRNAs (A) and miRNAs (B) was validated by performing quantitative real-time PCR on the normal peripheral blood monocytes from four healthy donors and the rheumatoid arthritis synovial fluid monocytes from twelve patients (RA1-RA12). The data is shown as means± SD. ∗p<0.05.

Reference

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