Abstract
MicroRNA (miRNA) is small RNA of 20 to 22 nucleotides in length and is stably present in plasma. Regulating the expression of miRNA taken into cells has been suggested as a general therapeutic approach. We identified the novel anti-inflammatory miRNA hsa-miR-766-3p and investigated its biological function in human rheumatoid arthritis (RA) fibroblast-like synoviocyte MH7A cells. To verify the function of the miRNA present in the plasma of RA patients, we performed a comprehensive analysis of the miRNA expression during abatacept treatment and identified eight miRNAs with significantly altered expression levels. Among these eight miRNAs, miR-766-3p was found to have a clear function. The expression of inflammatory genes in response to inflammatory stimuli was suppressed in MH7A transduced with miR-766-3p. We showed that miR-766-3p indirectly reduced the activation of NF-κB and clarified that this mechanism was partially involved in the reduction of the mineralocorticoid receptor expression. In addition, the inflammatory responses were suppressed in other types of cells. These results indicate the novel function of miR-766-3p, findings that may aid in the development of therapies to suppress inflammation, not only in RA but also in other diseases.
Highlights
MicroRNA is a non-coding RNA with a chain length of approximately 22 nucleotides and is known to control gene expression [1]
We investigated the changes in blood-circulating miRNAs in rheumatoid arthritis (RA) patients before and after treatment with abatacept, a biologic agent used for RA that consists of an extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the Fc portion of human immunoglobulin G1
Using an MH7A human synovial fibroblast cell line, eight miRNA mimics were screened for changes in their tumor necrosis factor-α (TNF-α)-induced inflammatory gene expression. miRNA-transfected MH7A cells were treated with TNF-α, and the expression of interleukin (IL)-1β, IL-6, IL-8, and MMP3 mRNAs was analyzed by quantitative polymerase chain reaction
Summary
MicroRNA (miRNA) is a non-coding RNA with a chain length of approximately 22 nucleotides and is known to control gene expression [1]. The function of such blood-circulating miRNAs is unclear. In response to pro-inflammatory mediators, most notably tumor necrosis factor-α (TNF-α), synoviocytes express tissue-degrading enzymes, such as matrix metalloproteinases (MMPs), and inflammatory cytokines and chemokines [6]. These inflammatory mediators from synoviocytes support the activation and differentiation of infiltrating immune cells [7]. We investigated the changes in blood-circulating miRNAs in RA patients before and after treatment with abatacept, a biologic agent used for RA that consists of an extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the Fc portion of human immunoglobulin G1. Using the synovial cell line, we investigated the function of blood-circulating miRNAs, a type of miRNA that demonstrates significant fluctuations. We attempted to elucidate whether this miRNA acts as an anti-inflammatory miRNA in various diseases
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