miR-155敲除小鼠乳腺癌肺转移模型的外周免疫细胞分型分析  

Analysis of peripheral immune cell typing in breast cancer lung metastasis model of miR-155 knockout mice

作　　者：孙晓东 谢丽霞 杜凯丽 许倩倩 桑明 SUN Xiaodong;XIE Lixia;DU Kaili;XU Qianqian;SANG Ming(Center for Translational Medicine,Xiangyang No.1 People's Hospital,Hubei University of Medicine,Xiangyang 441000,China)

机构地区：[1]湖北医药学院附属襄阳市第一人民医院转化医学中心,襄阳441000

出　　处：《中国免疫学杂志》2024年第3期484-490,共7页Chinese Journal of Immunology

基　　金：湖北省科技厅实验动物资源开发及利用项目(2020DFE025);襄阳市科技局医疗卫生领域科技计划重点项目(2020YL26);襄阳市第一人民医院科技创新项目(XYY2021M07)。

摘　　要：目的:以miR-155基因敲除(miR155^(-/-))小鼠为对象,比较其与C57BL/6J野生型(WT)小鼠乳腺癌肺转移模型的外周血免疫细胞分型。方法:生物信息学分析miR-155在乳腺癌组织和外周血清中的表达水平及与预后的关系;采用尾静脉注射方式建立小鼠乳腺癌肺转移模型,流式细胞术对外周血免疫细胞进行分型分析;通过病理检查观察肺组织肿瘤转移情况。结果:miR-155^(-/-)小鼠T细胞和单核细胞百分比较WT小鼠显著降低(P<0.05),髓源性抑制细胞(MDSCs)百分比显著升高(P<0.01),其中单核细胞亚群(M-MDSC)显著减少(P<0.05),粒细胞亚群(G-MDSC)显著增多(P<0.05);在乳腺癌肺转移模型中,miR155^(-/-)小鼠的T淋巴细胞较WT小鼠明显增多(P<0.05),NK细胞明显减少(P<0.05),中性粒细胞明显减少(P<0.001),T细胞中Th细胞明显减少(P<0.05),M-MDSCs显著减少(P<0.01),而G-MDSCs显著增多(P<0.01)。结论:miR-155基因缺失导致外周免疫细胞分型的显著差异,使小鼠更易发生乳腺癌肺转移。Objective:To establish a mouse model of breast cancer lung metastasis with miR-155 knockout(miR155^(-/-))mice,and to compare the difference of peripheral blood immune cell typing between miR155^(-/-)mice and C57BL/6J wide-type(WT)mice.Methods:Bioinformatics analysis was used to explore the expression level of miR-155 in breast cancer tissues and peripheral serum,and its relationship with prognosis.Mouse model of lung metastasis of breast cancer was established by tail vein injection;peripheral blood was collected for flow cytometry,and the immune cell typing was analyzed;the lung tissues were collected for immunohisto-chemical detection to observe the tumor metastasis.Results:Percentage of T lymphocytes and monocytes in peripheral blood of miR155^(-/-)mice was significantly decreased compared with WT mice(P<0.05),percentage of myeloid inhibitory cells(MDSCs)was increased significantly(P<0.05),in which the proportion of monocyte subsets(M-MDSC)was significantly decreased(P<0.05),while the proportion of granulocyte subsets(G-MDSC)was significantly increased(P<0.05).In lung metastasis model of breast can-cer,percentage of T lymphocytes in peripheral blood of miR155^(-/-)mice was significantly higher compared with WT mice,while per-centage of NK cells was decreased significantly(P<0.05),percentage of neutrophil was significantly decreased(P<0.001),propor-tion of Th cells in T lymphocytes was significantly decreased(P<0.05),proportion of M-MDSCs was significantly decreased(P<0.01),while proportion of G-MDSCs was significantly increased(P<0.01).Conclusion:Deletion of miR-155 gene leads to significant differences in peripheral immune cell typing,making mice more susceptible to lung metastasis of breast cancer.

关 键 词：MIR-155 基因敲除小鼠 乳腺癌 肺转移 外周血免疫分型 

分 类 号：R392.13[医药卫生—免疫学]