PMC:3218875 / 30218-32809 JSONTXT

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Notably, both miR-146 and miR-155 are expressed at higher levels in RA synovial fibroblasts and synovial tissue [81,82], as well as in peripheral blood mononuclear cells of RA patients [83]. miR-146a is also overexpressed in CD4+ and IL-17-producing T cells from RA patients [84,85]. Interestingly, a polymorphism in the 3'-UTR of the miR-146a target gene was recently shown to be associated with RA susceptibility [86]. miR-155 overexpression in synovial fibroblasts was able to prevent the TLR and cytokine-inducible expression of specific matrix metalloproteinases that mediate tissue destruction in RA [81]. Moreover, miR-155 was shown to promote TNF production, a key process in the pathogenesis of RA [87]. miR-146 and miR-155 may therefore be important negative regulators of inflammation in RA and their potential for the development of new treatments is substantial. In addition, their increased expression in RA patients is potentially useful as a marker for disease diagnosis, progression, or treatment efficacy [88], but this will require confirmation using a large and well-defined cohort.\nBesides miR-146 and miR-155, a number of other miRNAs with a potential role in the control of NF-κB-dependent inflammatory responses in RA pathology were recently identified. In this context, miR-124a - a key regulator of the chemokine monocyte chemoattractant protein 1 - was shown to be decreased in synoviocytes from RA patients [89]. Similarly, elevated levels of miR-203 - leading to increased secretion of matrix metalloproteinase-1 and IL-6 - were detected in RA synovial fibroblasts [90]. Finally, miR-16, miR-132, and miR-223 were also shown to have an altered expression in RA patients, indicating their potential as diagnostic biomarkers for pathogenesis 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