MicroRNAs (miRNAs) are a class of endogenous, highly conserved, small, non-coding RNAs that regulate gene expression at the post transcriptional level, and can act as key regulators of cellular mechanisms. Over the past years, dysregulation, malfunction or mutations of miRNAs have been described to be functionally involved in cancer as well as inmany other diseases. Therefore, the potential role of miRNAs linked with epigenetic modifications in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) is raising great expectations.
In the last years more and more publications have appeared showing that patients with RA are characterized by alterations in the expression of miRNAs. In this lecture we will focus on differentially expressed miRs in cells (peripheral blood cells such as T cells, synovial tissue, synovial fibroblasts) and body-fluids (sera and synovial fluid) of patients with RA. Based on the human TNF transgenic mouse model we will show how we could discover novel miRs (miR-221 and -223) associated with the pathogenesis of RA. Since one miR can regulate hundreds of genes we will explore the main function of specific miRs (miR-155) considering their phenotype in knock-out animals. Further, we will discuss how we can link the lack (miR-124 or -196) or over-expression (miR-155, -203) of miRs to inflammatory and immune processes in RA. Based on the fact that miRs are localized in microvesicles, bound to Argonaute proteins and/or high density lipoproteins (HDL) surprisingly miRs are of high stability in body fluids such as sera or synovial fluids and could serve as potential biomarkers. Finally we will discuss novel strategies to target miRs in the treatment of RA.
Disclosure of Interest None Declared
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