Department of Gynaecology and Obstetrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
Department of Pathology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
Biosci Rep. 2016 Aug 5;36(4). doi: 10.1042/BSR20160105. Print 2016 Aug.
Macrophages are highly plastic cells with the ability to differentiate into both M1- and M2-polarized phenotypes. As a distinct M2-polarized population, tumour-associated macrophages (TAMs) promote tumorigenesis owing to their pro-angiogenic and immune-suppressive functions in tumour microenvironment. In the present study, we found that the microRNA-720 (miR-720) was down-regulated in TAMs isolated from breast carcinomas and M2-polarization macrophages. Overexpression of miR-720 attenuated M2 phenotype expression and thus inhibited M2 polarization. We further identified GATA binding protein 3 (GATA3), a transcriptional factor that plays an important role in M2 macrophage polarization, was the downstream target of miR-720 Ectopic expression of GATA3 restored the M2 phenotype in miR-720 overexpressed macrophages. Importantly, overexpression of miR-720 inhibited pro-migration behaviour and phagocytic ability of M2-polarized macrophages. Thus, our data suggest that miR-720 plays an important role in regulating M2 macrophage polarization and function.
巨噬细胞是具有高度可塑性的细胞，能够分化为 M1 和 M2 极化表型。作为一种独特的 M2 极化群体，肿瘤相关巨噬细胞（TAMs）由于在肿瘤微环境中的促血管生成和免疫抑制功能而促进肿瘤发生。在本研究中，我们发现，从小鼠乳腺癌和 M2 极化巨噬细胞中分离的 TAMs 中，微 RNA-720（miR-720）表达下调。miR-720 的过表达减弱了 M2 表型的表达，从而抑制了 M2 极化。我们进一步鉴定出 GATA 结合蛋白 3（GATA3）是 M2 巨噬细胞极化中的重要转录因子，是 miR-720 的下游靶标。GATA3 的异位表达恢复了 miR-720 过表达巨噬细胞中的 M2 表型。重要的是，miR-720 的过表达抑制了 M2 极化巨噬细胞的迁移和吞噬能力。因此，我们的数据表明，miR-720 在调节 M2 巨噬细胞极化和功能方面发挥着重要作用。
