The pseudokinase TRIB1 controls cell function in a range of contexts, by regulating MAP kinase activation and mediating protein degradation via the COP1 ubiquitin ligase. TRIB1 regulates polarization of macrophages and dysregulated Trib1 expression in murine models has been shown to alter atherosclerosis burden and adipose homeostasis. Recently, TRIB1 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 TRIB1 itself remain elusive. Here, we show that the long and conserved 3’untranslated region (3’UTR) of TRIB1 is targeted by miRNAs in macrophage and prostate cancer models. By using a systematic in silico analysis, we identified multiple “high confidence” miRNAs potentially binding to the 3’UTR of TRIB1 and report that miR-101-3p and miR-132-3p are direct regulators of TRIB1 expression and function. Binding of miR-101-3p and miR-132-3p to the 3’UTR of TRIB1 mRNA leads to an increased transcription and secretion of interleukin-8. Our data demonstrate that modulation of TRIB1 by miRNAs alters the inflammatory profile of both human macrophages and prostate cancer cells.

假激酶 TRIB1 通过调节MAP激酶激活并介导蛋白质降解，在一定范围内控制细胞功能 通过 COP1泛素连接酶。 TRIB1调节巨噬细胞极化和鼠模型中Trib1表达失调可改变动脉粥样硬化负担和脂肪稳态。最近，TRIB1前列腺癌也与前列腺癌的发病机制有关，即使缺乏基因扩增，前列腺癌也经常被过度表达。在免疫细胞和癌变过程中，众所周知的TRIB1效应子包括MAP激酶和C / EBP转录因子。但是，调节的机制TRIB1本身仍然难以捉摸。在这里，我们显示了长而保守的3'非翻译区（3'UTR）TRIB1在巨噬细胞和前列腺癌模型中被miRNA靶向。通过使用系统在计算机上 分析中，我们发现了多个“高信度” miRNA，它们可能会与3'UTR结合 TRIB1 并报告说miR-101-3p和miR-132-3p是MRC的直接调节剂 TRIB1表达和功能。miR-101-3p和miR-132-3p与3'UTR的结合TRIB1mRNA导致白介素8的转录和分泌增加。我们的数据表明TRIB1 miRNA的作用改变了人类巨噬细胞和前列腺癌细胞的炎症状态。