J Immunol：MicroRNA-494对免疫细胞的募集至关重要

髓系来源抑制细胞(myeloid-derived suppressor cells，MDSCs)是未分化成熟的、异质性的、具有免疫抑制功能的髓系细胞群体。MDSCs能有效抑制抗肿瘤免疫反应，有利于肿瘤的血管生成和转移的肿瘤微环境。

到目前为止，肿瘤调节MDSCs的聚集功能分子网络在很大程度上是未知的。近日，Liu Y, 等研究人员在J Immunol杂志上发表论文称microRNA-494的表达能显著诱导MDSCs的聚集microRNA-494主要来源于肿瘤细胞。其机制就是调控张力蛋白同源物（PTEN）和Akt信号途径。

研究发现TGF-β1主要负责上调肿瘤衍生因子miR-494的表达。miR-494的表达不仅增强CXCR4介导的MDSC趋化作用，也改变肿瘤细胞内在的凋亡/生存信号，促进MDSCs在肿瘤组织中积累。

因此，PTEN的下调激活Akt信号途径能促进肿瘤细胞的浸润和转移。体内实验中抑制miR-494将大大扭转了MDSCs的活动，进而抑制肿瘤的生长。总的来说，研究结果表明，TGF-β1诱导miR-494的表达导致MDSCs在肿瘤组织中积累，这一结果提示MicroRNA-494可能是一种治疗癌症的潜在新靶标。

doi:10.4049/jimmunol.1103505
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MicroRNA-494 Is Required for the Accumulation and Functions of Tumor-Expanded Myeloid-Derived Suppressor Cells via Targeting of PTEN.

Liu Y, Lai L, Chen Q, Song Y, Xu S, Ma F, Wang X, Wang J, Yu H, Cao X, Wang Q.

Myeloid-derived suppressor cells (MDSCs) potently suppress the anti-tumor immune responses and also orchestrate the tumor microenvironment that favors tumor angiogenesis and metastasis. The molecular networks regulating the accumulation and functions of tumor-expanded MDSCs are largely unknown. In this study, we identified microRNA-494 (miR-494), whose expression was dramatically induced by tumor-derived factors, as an essential player in regulating the accumulation and activity of MDSCs by targeting of phosphatase and tensin homolog (PTEN) and activation of the Akt pathway. TGF-β1 was found to be the main tumor-derived factor responsible for the upregulation of miR-494 in MDSCs. Expression of miR-494 not only enhanced CXCR4-mediated MDSC chemotaxis but also altered the intrinsic apoptotic/survival signal by targeting of PTEN, thus contributing to the accumulation of MDSCs in tumor tissues. Consequently, downregulation of PTEN resulted in increased activity of the Akt pathway and the subsequent upregulation of MMPs for facilitation of tumor cell invasion and metastasis. Knockdown of miR-494 significantly reversed the activity of MDSCs and inhibited the tumor growth and metastasis of 4T1 murine breast cancer in vivo. Collectively, our findings reveal that TGF-β1-induced miR-494 expression in MDSCs plays a critical role in the molecular events governing the accumulation and functions of tumor-expanded MDSCs and might be identified as a potential target in cancer therapy.