miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer.

miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer.
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miRNA let-7b 调节巨噬细胞极化并增强肿瘤相关巨噬细胞以促进前列腺癌的血管生成和迁移

DOI:
10.1038/srep25602
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发表时间:
2016-05-09
期刊:
影响因子:
4.6
通讯作者:
Min W
Min W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang Z;Xu L;Hu Y;Huang Y;Zhang Y;Zheng X;Wang S;Wang Y;Yu Y;Zhang M;Yuan K;Min W

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巨噬细胞极化是一种高度可塑性的生理过程,通过改变巨噬细胞表型和功能来响应各种环境因素。肿瘤相关巨噬细胞(TAM)通常被认为可以促进肿瘤进展。作为通用调节因子,microRNA (miRNA) 在功能上参与许多关键的细胞过程,包括巨噬细胞极化。 Let-7b 是一种 miRNA,与健康对照相比,在发炎组织中具有差异表达模式。然而,miRNA let-7b 是否以及如何调节巨噬细胞表型和功能尚不清楚。在本报告中,我们发现let-7b的上调是前列腺TAM的特征,而TAM中let-7b的下调会导致炎症细胞因子(例如IL-12、IL-23、IL-10和TNF-α)表达谱的变化。因此,用 let-7b 抑制剂处理的 TAM 会减少血管生成和前列腺癌 (PCa) 细胞的迁移性。 Let-7b可能在调节巨噬细胞极化中发挥重要作用,从而调节前列腺癌的预后。
Macrophage polarization is a highly plastic physiological process that responds to a variety of environmental factors by changing macrophage phenotype and function. Tumor-associated macrophages (TAMs) are generally recognized as promoting tumor progression. As universal regulators, microRNAs (miRNAs) are functionally involved in numerous critical cellular processes including macrophage polarization. Let-7b, a miRNA, has differential expression patterns in inflamed tissues compared with healthy controls. However, whether and how miRNA let-7b regulates macrophage phenotype and function is unclear. In this report, we find that up-regulation of let-7b is characteristic of prostatic TAMs and down-regulation of let-7b in TAMs leads to changes in expression profiles of inflammatory cytokines, such as IL-12, IL-23, IL-10 and TNF-α. As a result, TAMs treated with let-7b inhibitors reduce angiogenesis and prostate carcinoma (PCa) cell mobility. Let-7b may play a vital role in regulating macrophage polarization, thus modulating the prognosis of prostate cancer.