Mouse peritoneal macrophages treated with LPS for 6 hours

MicroRNA Let-7 has abundant expression in macrophages and can repress the expression of IL-6 via binding the 3'UTR of IL-6 mRNA. Here, the IL-6 ceRNAs, which compete let-7 with IL-6, was investigated by cDNA Microarray. We reveal that RasGRP1 specifically derepress the expression of IL-6 by competing Let-7a in inflammatory response. Our data elucidated a previously uncharacterized coding-independent role of RasGRP1 in innate immunity, providing an insight into the ceRNAs modulation of innate immune response, and found that RasGRP1 have a dual-function in promoting inflammation and inhibiting tumor by a protein-independent or dependent manner respectively, which may well explain why acute inflammation rarely leads to tumorigenesis. Comparison the expression level of Let7 target-genes in LPS or PBS treated macrophages.

微RNA（microRNA）Let-7在巨噬细胞中表达丰富，可通过结合白细胞介素6（IL-6）信使RNA（mRNA）的3'非翻译区（3'UTR）抑制IL-6的表达。本研究借助cDNA微阵列（cDNA Microarray），对可与IL-6竞争结合Let-7的内源竞争RNA（ceRNAs，competing endogenous RNAs）展开了探究。研究发现，Ras鸟苷酸释放蛋白1（RasGRP1）可在炎症反应中通过竞争结合Let-7a，特异性解除IL-6的表达抑制。本研究阐明了RasGRP1此前未被揭示的、不依赖编码功能的固有免疫调控新功能，为内源竞争RNA调控固有免疫应答提供了新的研究视角；同时发现RasGRP1可分别通过不依赖蛋白与依赖蛋白的方式，发挥促炎与抑癌的双重功能，这一发现或可解释急性炎症极少引发肿瘤发生的原因。此外，本研究还对比了脂多糖（LPS）或磷酸盐缓冲液（PBS）处理的巨噬细胞中Let-7靶基因的表达水平。