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IRF4过表达促进调节性T细胞向巨噬细胞样细胞转分化，从而抑制结肠癌的发展。

IRF4 overexpression promotes the transdifferentiation of tregs into macrophage-like cells to inhibit the development of colon cancer.

作者信息

Wang Jiwei, Li Song, Li Honglang, Zhou Xiaoshuang, Wen Huabin, Lai Bin

机构信息

Department of Ultrasound, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

Mudanjiang Medical College, Mudanjiang, Heilongjiang, China.

出版信息

Cancer Cell Int. 2021 Jan 19;21(1):58. doi: 10.1186/s12935-021-01766-6.

DOI:10.1186/s12935-021-01766-6
PMID:33468159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7816309/
Abstract

BACKGROUND

Interferon regulatory factor 4 (IRF4) is a transcription factor from the IRF factor family that exerts regulatory functions in the immune system and oncogenesis. However, the biological role of IRF4 in colon cancer is still unclear. The aim of this study is to investigate whether IRF4 participates in the immune response in colon cancer.

METHODS

We compared the expression of IRF4, the number of regulatory T cells (Tregs) and macrophages in the colon cancer tissues and paracancerous colon tissues from colon cancer patients. Colon cancer mouse model was established by inoculation with colon cancer cells (SW480) as a xenograft tumor, and we observed tumor growth of colon cancer. Furthermore, the mechanism of action of IRF4 in transdifferentiation of Tregs into macrophage-like cells and the effect of IRF4 on colon cancer cells were investigated in vitro.

RESULTS

IRF4 was severely down-regulated in the colon cancer tissues. Colon cancer tissues exhibited an increase in the number of regulatory T cells (Tregs) and macrophages. Furthermore, IRF4 overexpression repressed proliferation, migration and invasion of colon cancer cells (SW480 and HT116 cells). Moreover, IRF4 up-regulation ameliorated tumor growth of colon cancer by promoting the transdifferentiation of Tregs into macrophage-like cells through inhibition of BCL6 expression. Exosomes derived from colon cancer cells repressed IRF4 expression in Tregs by transmitting miR-27a-3p, miR-30a-5p and miR-320c.

CONCLUSIONS

IRF4 overexpression promoted the transdifferentiation of Tregs into macrophage-like cells to inhibit the occurrence and development of colon cancer. Thus, IRF4 may be a potential target for colon cancer treatment.

摘要

背景

干扰素调节因子4（IRF4）是IRF因子家族的转录因子，在免疫系统和肿瘤发生过程中发挥调节功能。然而，IRF4在结肠癌中的生物学作用仍不清楚。本研究旨在探讨IRF4是否参与结肠癌的免疫反应。

方法

我们比较了结肠癌患者结肠癌组织和癌旁结肠组织中IRF4的表达、调节性T细胞（Tregs）和巨噬细胞的数量。通过接种结肠癌细胞（SW480）作为异种移植瘤建立结肠癌小鼠模型，并观察结肠癌的肿瘤生长情况。此外，在体外研究了IRF4在Tregs向巨噬细胞样细胞转分化中的作用机制以及IRF4对结肠癌细胞的影响。

结果

IRF4在结肠癌组织中严重下调。结肠癌组织中调节性T细胞（Tregs）和巨噬细胞的数量增加。此外，IRF4过表达抑制结肠癌细胞（SW480和HT116细胞）的增殖、迁移和侵袭。而且，IRF4上调通过抑制BCL6表达促进Tregs向巨噬细胞样细胞转分化，从而改善结肠癌的肿瘤生长。源自结肠癌细胞的外泌体通过传递miR-27a-3p、miR-30a-5p和miR-320c抑制Tregs中IRF4的表达。

结论

IRF4过表达促进Tregs向巨噬细胞样细胞转分化，从而抑制结肠癌的发生和发展。因此，IRF4可能是结肠癌治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/99c087e974a4/12935_2021_1766_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/e8d92189b557/12935_2021_1766_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/7e1dc44a356a/12935_2021_1766_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/93b7dcace7a9/12935_2021_1766_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/d819cfe40c9a/12935_2021_1766_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/ef91ef260b84/12935_2021_1766_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/16a328c28bc0/12935_2021_1766_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/b17997a0805b/12935_2021_1766_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/3600c0e06433/12935_2021_1766_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/99c087e974a4/12935_2021_1766_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/e8d92189b557/12935_2021_1766_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/7e1dc44a356a/12935_2021_1766_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/93b7dcace7a9/12935_2021_1766_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/d819cfe40c9a/12935_2021_1766_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/ef91ef260b84/12935_2021_1766_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/16a328c28bc0/12935_2021_1766_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/b17997a0805b/12935_2021_1766_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/3600c0e06433/12935_2021_1766_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/7816309/99c087e974a4/12935_2021_1766_Fig9_HTML.jpg

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