miR-181a Induces Macrophage Polarized to M2 Phenotype and Promotes M2 Macrophage-mediated Tumor Cell Metastasis by Targeting KLF6 and C/EBPα.
miR-181a Induces Macrophage Polarized to M2 Phenotype and Promotes M2 Macrophage-mediated Tumor Cell Metastasis by Targeting KLF6 and C/EBPα.
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miR-181a 通过靶向 KLF6 和 C/EBPα 诱导巨噬细胞极化为 M2 表型并促进 M2 巨噬细胞介导的肿瘤细胞转移。
DOI：
10.1038/mtna.2016.71
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发表时间：
2016-09-27
期刊：
影响因子：
--
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中科院分区：
文献类型：
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巨噬细胞可以获得多种极化状态和功能：经典激活巨噬细胞（M1巨噬细胞）；替代激活的巨噬细胞（M2 巨噬细胞）。然而，该过程的分子基础仍不清楚。本研究指出 microRNA-181a (miR-181a) 是控制巨噬细胞极化的关键分子。我们发现 miR-181a 在 M2 巨噬细胞中比在 M1 巨噬细胞中过表达。当M2表型转变为M1时，miR-181a表达降低，而当M1表型转变为M2时，miR-181a表达增加。 M1 巨噬细胞中 miR-181a 的过度表达减少了 M1 表型表达，同时促进了向 M2 表型的极化。相反，M2巨噬细胞中miR-181a的敲除促进了M1极化并减少了M2表型表达。从机制上讲，生物信息学分析表明，Kruppel 样因子 6 (KLF6) 和 CCAAT/增强子结合蛋白-α (C/EBPα) 是 miR-181a 的潜在靶标，荧光素酶测定证实，KLF6 和 C/EBPα 翻译通过与 KLF6 和 C/EBPα mRNA 的 3'UTR 相互作用而被 miR-181a 抑制。进一步分析表明，miR-181a 的诱导抑制了 KLF6 和 C/EBPα 蛋白的表达。重要的是，miR-181a 还会降低 M2 巨噬细胞介导的肿瘤细胞迁移和侵袭能力。总的来说，我们的结果表明 miR-181a 通过直接靶向 KLF6 和 C/EBPα 在调节巨噬细胞极化中发挥重要作用。
Macrophages can acquire a variety of polarization status and functions: classically activated macrophages (M1 macrophages); alternatively activated macrophages (M2 macrophages). However, the molecular basis of the process is still unclear. Here, this study addresses that microRNA-181a (miR-181a) is a key molecule controlling macrophage polarization. We found that miR-181a is overexpressed in M2 macrophages than in M1 macrophages. miR-181a expression was decreased when M2 phenotype converted to M1, whereas it increased when M1 phenotype converted to M2. Overexpression of miR-181a in M1 macrophages diminished M1 phenotype expression while promoting polarization to the M2 phenotype. In contrast, knockdown of miR-181a in M2 macrophages promoted M1 polarization and diminished M2 phenotype expression. Mechanistically, Bioinformatic analysis revealed that Kruppel-like factor 6 (KLF6) and CCAAT/enhancer binding protein-α (C/EBPα) is a potential target of miR-181a and luciferase assay confirmed that KLF6 and C/EBPα translation is suppressed by miR-181a through interaction with the 3′UTR of KLF6 and C/EBPα mRNA. Further analysis showed that induction of miR-181a suppressed KLF6 and C/EBPα protein expression. Importantly, miR-181a also diminishes M2 macrophages-mediated migration and invasion capacity of tumor cells. Collectively, our results suggest that miR-181a plays a significant role in regulating macrophage polarization through directly target KLF6 and C/EBPα.
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影响因子：
3.8
作者：
Jia, Xuemei;Yu, Fang;Wang, Junfeng;Iwanowycz, Stephen;Saaoud, Fatma;Wang, Yuzhen;Hu, Jun;Wang, Qian;Fan, Daping
通讯作者：
Fan, Daping
肺瘤平膏通过抑制肿瘤炎症微环境抑制肺癌生长和侵袭
影响因子：
--
作者：
Li W;Chen C;Saud SM;Geng L;Zhang G;Liu R;Hua B
通讯作者：
Hua B
DOI：
10.4049/jimmunol.1202496
发表时间：
2013-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Banerjee S;Xie N;Cui H;Tan Z;Yang S;Icyuz M;Abraham E;Liu G
通讯作者：
Liu G
影响因子：
8
作者：
Cardoso, A. P.;Pinto, M. L.;Oliveira, M. J.
通讯作者：
Oliveira, M. J.
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia