Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells

The pseudokinase controls cell function in a range of contexts, by regulating MAP kinase activation and mediating protein degradation the COP1 ubiquitin ligase. regulates polarization of macrophages and dysregulated Trib1 expression in murine models has been shown to alter atherosclerosis burden and adipose homeostasis. Recently, has also been implicated in the pathogenesis of prostate cancer, where it is often overexpressed, even in the absence of genetic amplification. Well described TRIB1 effectors include MAP kinases and C/EBP transcription factors, both in immune cells and in carcinogenesis. However, the mechanisms that regulate itself remain elusive. Here, we show that the long and conserved 3'untranslated region (3'UTR) of is targeted by miRNAs in macrophage and prostate cancer models. By using a systematic analysis, we identified multiple "high confidence" miRNAs potentially binding to the 3'UTR of and report that miR-101-3p and miR-132-3p are direct regulators of expression and function. Binding of miR-101-3p and miR-132-3p to the 3'UTR of mRNA leads to an increased transcription and secretion of interleukin-8. Our data demonstrate that modulation of by miRNAs alters the inflammatory profile of both human macrophages and prostate cancer cells.