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

Mesenchymal Stem Cell-Derived Exosomal miRNA-222-3p Increases Th1/Th2 Ratio and Promotes Apoptosis of Acute Myeloid Leukemia Cells.

机构信息

Department of Hematology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.

Department of Hematology, Bengbu Medical College, Bengbu, Anhui 233004, China.

出版信息

Anal Cell Pathol (Amst). 2023 Aug 16;2023:4024887. doi: 10.1155/2023/4024887. eCollection 2023.

DOI:10.1155/2023/4024887
PMID:37621743
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10447000/
Abstract

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 and . The contents of Interferon (IFN-) 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 . 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.

摘要

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）衍生的外泌体可以分泌 mRNA、miRNA 和蛋白质来调节肿瘤微环境。本研究主要关注 miRNA/IRF2 轴在调节急性髓系白血病（AML）中 Th1/Th2 比值和细胞凋亡中的作用。通过流式细胞术分析检测 Th1/Th2 比值和 AML 细胞凋亡，并用酶联免疫吸附试验检测干扰素-（IFN-）和白细胞介素-4（IL-4）的含量。利用 StarBase 预测 miR-222-3p 与 IRF2 3'UTR 之间的潜在结合位点。通过荧光素酶报告基因实验验证 miR-222-3p 与 IRF2 的结合。成功分离了 BM-MSC 外泌体。BM-MSC 外泌体增加了 Th1/Th2 比值并促进了 AML 细胞凋亡。进一步分析表明，IRF2 是 miR-222-3p 的靶基因。miR-222-3p 的过表达促进了 Th1/Th2 比值和 AML 细胞凋亡。IRF2 部分逆转了 miR-222-3p 对 Th1/Th2 比值和 AML 细胞凋亡的作用。miR-222-3p 的过表达促进了 Th1/Th2 比值和半胱天冬酶 3 的表达。综上所述，miR-222-3p 通过调节 IRF2 的表达促进 Th1/Th2 比值和 AML 细胞凋亡，为 AML 的治疗提供了重要的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/09aed1e6e572/ACP2023-4024887.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/f2fafae1098b/ACP2023-4024887.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/96ea27a5d0ac/ACP2023-4024887.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/e20b7c4868cb/ACP2023-4024887.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/e7445f3eb301/ACP2023-4024887.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/09aed1e6e572/ACP2023-4024887.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/f2fafae1098b/ACP2023-4024887.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/96ea27a5d0ac/ACP2023-4024887.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/e20b7c4868cb/ACP2023-4024887.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/e7445f3eb301/ACP2023-4024887.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/10447000/09aed1e6e572/ACP2023-4024887.005.jpg

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本文引用的文献

[1]
The IRF2/CENP-N/AKT signaling axis promotes proliferation, cell cycling and apoptosis resistance in nasopharyngeal carcinoma cells by increasing aerobic glycolysis.

J Exp Clin Cancer Res. 2021-12-10

[2]
Prognostic and Immune-Infiltrate Significance of miR-222-3p and Its Target Genes in Thyroid Cancer.

Front Genet. 2021-10-19

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Onco Targets Ther. 2021-9-24

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Front Oncol. 2021-4-15

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Exp Hematol Oncol. 2021-3-31

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IRF2 regulates cellular survival and Lenvatinib-sensitivity of hepatocellular carcinoma (HCC) through regulating β-catenin.

Transl Oncol. 2021-6

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Microvasc Res. 2021-5

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Cell Mol Immunol. 2021-3

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Cancer Cell Int. 2020-5-19

[10]
miR-221-3p and miR-222-3p downregulation promoted osteogenic differentiation of bone marrow mesenchyme stem cells through IGF-1/ERK pathway under high glucose condition.

Diabetes Res Clin Pract. 2020-3-16

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