MicroRNAs modulate the noncanonical transcription factor NF-kappaB pathway by regulating expression of the kinase IKKalpha during macrophage differentiation.
MicroRNAs modulate the noncanonical transcription factor NF-kappaB pathway by regulating expression of the kinase IKKalpha during macrophage differentiation.
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microRNA是许多生物过程包括细胞分化的关键调节因子。在这里，我们发现在人类单核细胞-巨噬细胞分化过程中，microRNAs miR-223、miR-15 a和miR-16的表达显著降低，导致巨噬细胞中丝氨酸-苏氨酸激酶IKKα的表达增加。在巨噬细胞中，IKKα的高表达与激酶NIK的稳定性结合诱导p52升高。由于未处理的巨噬细胞中RelB转录因子表达较低，p52高表达抑制了经典和非经典NF-κB靶基因的基础水平。然而，巨噬细胞中的促炎刺激导致非经典NF-κB靶基因的更大诱导。因此，某些microRNA的减少可能会防止巨噬细胞过度活动，但会引发巨噬细胞对促炎刺激的某些反应。
MicroRNAs are key regulators in many biological processes including cell differentiation. Here we show that during human monocyte-macrophage differentiation, the expression of the microRNAs miR-223, miR-15a, and miR-16 is dramatically decreased, leading to increased expression of the serine-threonine kinase IKKα in macrophages. In macrophages, higher IKKα expression in conjunction with stabilization of the kinase NIK induces elevated p52. Due to low RelB transcription factor expression in untreated macrophages, high p52 expression represses the basal level of both canonical and noncanonical NF-κB target genes. However, proinflammatory stimuli in macrophages result in greater induction of noncanonical NF-κB target genes. Thus a decrease in certain microRNAs likely prevents macrophage hyperaction yet primes the macrophage for certain responses to proinflammatory stimuli.