Dysregulation of miR-155-5p and miR-200-3p and the Anti-Non-Bilayer Phospholipid Arrangement Antibodies Favor the Development of Lupus in Three Novel Murine Lupus Models

Figure 4

miR-155-5p and miR-200a-3p greatly influence TLR4 signaling pathways. miR-155-5p and miR-200a-3p targets were obtained and analyzed using the database of the Cancer miRNA Regulatory Network [19] along with Cytoscape v3.4.0 [18]. The overall effect of miR-155-5p downregulation and miR-200a-3p upregulation is an increased transcription of INFA1 and INFA2. Here, the two canonical signaling pathways triggered by TLR4 activation are shown, one through MYD-88 (with the final production of NFκB and AP-1 transcription factors) and the other through TICAMs (and production of IRF-3 transcription factor). A close analysis reveals that miR-200a-3p inhibits the production of AP-1 from MYD88, downregulating that pathway, while miR-155-5p is positively affecting interferon expression by activating a series of transcription factors. Red boxes indicate our previously described findings [6], and dotted rectangles highlight the transcription factors directly targeted by these miRNA and directly related to interferon gene expression.