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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 aimed to investigate the mechanism of miRNAs in inhibiting the activation of CD4 ~ + T cells by Cbl-b. The levels of Cbl-b ~ (+) - CD4 ~ + T cells, anti-CD3 antibody-activated WT CD4 ~ + T cells and anti-CD3 antibody were detected by miRNA- (- / -) miRNA expression profiles in CD4 ~ + T cells. The results showed that miR-125b-2-3p, miR-125b-5p, miR-99a-5p and miR-99a-3p were activated by both Cbl-b - / - CD4 ~ + T cells and anti-CD3 antibodies ~ (- / -) CD4 ~ + T cells were significantly higher expression. Using miRWalk2.0 to predict differentially expressed miRNA target genes and analyze the possible mechanism of differentially expressed miRNA using GO and KEGG. The results showed that differentially expressed miRNAs may affect the activation of CD4 ~ + T cells by Cbl-b via MAPK signaling pathway. In summary, Cbl-b may inhibit MAPK and other signaling pathways through miR-125b-2-3p, miR-125b-5p, miR-99a-5p and miR-99a-3p miRNAs to inhibit CD4 ~ + T cell activation.