Association of XIST/miRNA155/Gab2/TAK1 cascade with the pathogenesis of anti-phospholipid syndrome and its effect on cell adhesion molecules and inflammatory mediators

Figures

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  Figure 1. Comparison of gene expression profiles of lncRNA XIST (A) and miRNA155 (B) between healthy subjects, primary and secondary APS patients. Spearman correlation between XIST and miRNA155 among primary (C) and secondary (D) APS patients. (E) Putative binding sites were detected between XIST (target sequences labeled with blue) and miRNA155 (at seed sequence labeled with red) using a transcriptome-wide microRNA target prediction tool (www.mircode.org). (A–B)The box represents the 25–75% percentiles; the line inside the box represents the median and the error bars lines represent the 10–90% percentiles. * Significance difference with the control group. # Significance difference with primary APS.

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  Figure 2. Comparison of the relative gene expression of Gab2 (A) and TAK1 (B) as well as relative protein expression of Gab2 (C) and TAK1 (D) between healthy subjects, primary and secondary APS groups. (A–B) The box represents the 25–75% percentiles; the line inside the box represents the median and the error bars represent the 10–90% percentiles. (C–D) Data are represented as mean ± SD. (E) Representative blots of Gab2 and TAK1. ꞵ actin was used as the loading control. Data are represented as mean ± SD. Gab2: Grb2-associated binding, TAK1: Transforming growth factor beta-activated kinase 1. * Significance difference with the control group. # Significance difference with primary APS.

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  Figure 3. Serum levels of VCAM-1 (A), ICAM-1 (B), IL-1ꞵ (C), and TNF-α (D) among healthy subjects, primary and secondary APS groups. Data are represented as mean ± SD. ICAM-11: Intracellular cell adhesion molecules, IL-1ꞵ: Interleukin1ꞵ, TNF-α: Tumor necrosis factor-α, VCAM-1: Vascular cell adhesion molecules. *Significance difference with the control group. # Significance difference with primary APS.

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  Figure 4. Double gradient heat map graph representing the correlations between different studied parameters in primary (A) and secondary (B) APS patients. Blue color represents the strong positive correlation (1), while yellow color represents the negative correlation (− 1). Gab2: Grb2-associated binding, ICAM-1: Intracellular cell adhesion molecules, IL-1ꞵ: Interleukin1ꞵ, TAK1: Transforming growth factor beta-activated kinase 1, TNF-α: Tumor necrosis factor-α, VCAM-1: Vascular cell adhesion molecules.

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  Figure 5. Integrated network representing the interaction between the studied genes. Gab2: Grb2-associated binding, ICAM-1: Intracellular cell adhesion molecules, IL-1ꞵ: Interleukin1ꞵ, MAP3K7 /9TAK1): Transforming growth factor beta-activated kinase 1, TNF-α: Tumor necrosis factor-α, VCAM-1: Vascular cell adhesion molecules.

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  Figure 6. ROC curve to predict the diagnostic performance of XIST and miRNA155 in predicting primary and secondary APS, as well as miscarriage events.

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  Figure 7. Gene ontology analysis of the examined pathway. (A) Biological processes domain, (B) Molecular function domain. (C) Data relevant to KEGG pathways. Data are sorted based on fold enrichment.