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. 2013 Mar 19:4:70.
doi: 10.3389/fimmu.2013.00070. eCollection 2013.

The miR-17 ∼ 92 Cluster: A Key Player in the Control of Inflammation during Rheumatoid Arthritis

Lucas Philippe  1 , Ghada Alsaleh, Seiamak Bahram, Sébastien Pfeffer, Philippe Georgel
Affiliations

The miR-17 ∼ 92 Cluster: A Key Player in the Control of Inflammation during Rheumatoid Arthritis

Lucas Philippe et al. Front Immunol. .

Abstract

MicroRNAs (miRNAs) are now recognized as essential regulators of gene expression in plants and animals. They potentially modulate the expression of multiple genes thereby enabling homeostatic settings in physiological conditions. Their role is also increasingly considered in many diseases in which deregulated epigenetic mechanisms induce aberrant gene expression. Work conducted in our laboratory has recently led to the identification of miRNAs essential for the control of inflammatory reactions that occur during rheumatoid arthritis (RA). In this review, we describe two such miRNAs, members of the miR-17 ∼ 92 cluster, which has been previously implicated in cancer. Based on our data and on predicted miRNA:mRNA interactions, we will extrapolate a model whereby the miR-17 ∼ 92 cluster appears as a global regulator of the Apoptosis Signal-Regulating Kinase 1 signalosome, a central actor in the inflammatory pathways activated during RA. We will also discuss the potential therapeutic outcomes emerging from this model.

Keywords: ASK1; TLR; inflammation; miR-17 ∼ 92; miRNA cluster; rheumatoid arthritis.

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Figures

Figure 1
Figure 1
Global targeting of the ASK1 signalosome by members of the miR-17 ∼ 92 cluster. The individual miRNAs encoded in the cluster are represented by boxes whose color corresponds to the components of the ASK1 signalosome that they are predicted to target. Proteins shown in blue (TLR4, Trx, TRAF2, and TRAF6) do not contain miRNA-binding sites for members of the cluster miR-17 ∼ 92 in their 3′UTR.
See this image and copyright information in PMC

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