Interferon regulatory factor 2 (IRF2) participates in the differentiation of immune T cells. Bone marrow mesenchymal stem cell (BM-MSC)-derived exosomes can secret mRNA, miRNAs, and proteins to regulate tumor microenvironment. The present study focused on the miRNA/IRF2 axis in regulating Th1/Th2 ratio and cell apoptosis in acute myeloid leukemia (AML). The flow cytometry analysis was performed to examine the Th1/Th2 ratio and AML apoptosis in vivo and in vitro. The contents of Interferon γ (IFN-γ) and Interleukin-4 (IL-4) were measured using enzyme-linked immunosorbent assay. StarBase was used to predict the potential binding site between miR-222-3p and the 3 untranslated region of IRF2. Luciferase reporter assay was applied for validating the combination of miR-222-3p and IRF2. BM-MSC exosomes were successfully isolated. BM-MSC exosomes increased Th1/Th2 ratio and promoted apoptosis of AML cells. Further analysis showed that IRF2 was targeted by miR-222-3p. Overexpression of miR-222-3p promoted Th1/Th2 ratio and AML cell apoptosis. IRF2 partially reversed the effect that is exerted by miR-222-3p on Th1/Th2 ratio and AML cell apoptosis. Overexpression of miR-222-3p promoted Th1/Th2 ratio and caspase 3 expression in vivo. To sum up, miR-222-3p promotes Th1/Th2 ratio and AML cell apoptosis by regulating IRF2 expression, which provided crucial targets for the treatment of AML.

中文翻译：

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间充质干细胞来源的外泌体 miRNA-222-3p 增加 Th1/Th2 比率并促进急性髓系白血病细胞凋亡

干扰素调节因子2（IRF2）参与免疫T细胞的分化。骨髓间充质干细胞 (BM-MSC) 来源的外泌体可以分泌 mRNA、miRNA 和蛋白质来调节肿瘤微环境。本研究重点关注 miRNA/IRF2 轴在急性髓系白血病 (AML) 中调节 Th1/Th2 比例和细胞凋亡的作用。采用流式细胞术分析体内外Th1/Th2比值和AML细胞凋亡情况。采用酶联免疫吸附法测定干扰素γ（IFN - γ ）和白细胞介素4（IL-4）的含量。StarBase 用于预测 miR-222-3p 与IRF2 3 个非翻译区之间的潜在结合位点。应用荧光素酶报告基因测定来验证 miR-222-3p 和 IRF2 的组合。成功分离BM-MSC外泌体。BM-MSC 外泌体增加 Th1/Th2 比率并促进 AML 细胞凋亡。进一步分析表明IRF2是miR-222-3p的靶标。miR-222-3p 的过表达促进 Th1/Th2 比率和 AML 细胞凋亡。IRF2 部分逆转了 miR-222-3p 对 Th1/Th2 比率和 AML 细胞凋亡的影响。miR-222-3p的过表达促进体内Th1/Th2比值和caspase 3表达。综上所述，miR-222-3p通过调节IRF2表达促进Th1/Th2比值和AML细胞凋亡，为AML的治疗提供了重要靶点。