MiRNA在E3泛素连接酶Cbl-b抑制CD4^+T细胞活化中的作用研究

E3 ubiquitin ligase Cbl-b inhibits the activation of CD4^+T cells through miRNAs

本研究探讨miRNA在Cbl-b抑制CD4^+T细胞活化中的作用机制。采用miRNA深度测序的方法检测WT CD4^+T细胞、Cbl^(-b-)/-CD4^+T细胞、抗CD3抗体活化的WT CD4^+T细胞和抗CD3抗体活化的Cbl-b^(-/-)CD4^+T细胞中miRNA的表达谱。结果显示,miR-125b-2-3p、miR-125b-5p、miR-99a-5p和miR-99a-3p同时在Cbl-b-/-CD4^+T细胞和抗CD3抗体活化的Cbl-b^(-/-)CD4^+T细胞中显著高表达。运用miRWalk2.0预测差异表达miRNA的靶基因并用GO和KEGG分析差异表达的miRNA的可能作用机制。结果显示差异表达的miRNA可能通过MAPK等信号通路来影响Cbl-b抑制CD4^+T细胞的活化。综上所述,Cbl-b可能通过miR-125b-2-3p、miR-125b-5p、miR-99a-5p和miR-99a-3p等miRNA调控MAPK等信号通路来抑制CD4^+T细胞的活化。

This study was undertaken to investigate the function of miRNA in the inhibition of CD4~＋T cells activation by Cblb.Firstly,we examined the expression profiles of miRNAs in WT CD4~＋T cells,Cbl-b-/-CD4~＋T cells,CD3 antibody activated WT CD4~＋T cells and CD3 antibody activated Cbl^（-b-）/-CD4~＋T cells by high-throughput small RNA deep sequencing.The results showed that miR-125 b-2-3 p,miR-125 b-5 p,miR-99 a-5 p and miR-99 a-3 p were significantly increased both in Cbl-b-/-CD4~＋T cells and anti-CD3 antibody activated Cbl-b^（-/-）CD4~＋T cells.The targets of differently expressed miRNAs were predicted by using miRWalk2.0 software.The potential mechanisms of differently expressed miRNAs were analyzed by GO and KEGG analysis,which suggested that Cbl-b may inhibit CD4~＋T cells activation by regulating the expressions of miRNAs to interfere with the MAPK and other signaling pathways.In conclusion,Cbl-b inhibits the CD4~＋T cell activation through miRNAs including miR-125 b-2-3 p,miR-125 b-5 p,miR-99 a-5 p and miR-99 a-3 p,thus,interferes MAPK and other signaling pathways.