髓系來源抑制細胞(myeloid-derived suppressor cells,，MDSCs)是未分化成熟的、異質(zhì)性的,、具有免疫抑制功能的髓系細胞群體,。MDSCs能有效抑制抗腫瘤免疫反應(yīng)，有利于腫瘤的血管生成和轉(zhuǎn)移的腫瘤微環(huán)境,。
到目前為止,，腫瘤調(diào)節(jié)MDSCs的聚集功能分子網(wǎng)絡(luò)在很大程度上是未知的。近日,，Liu Y, 等研究人員在J Immunol雜志上發(fā)表論文稱microRNA-494的表達能顯著誘導(dǎo)MDSCs的聚集microRNA-494主要來源于腫瘤細胞,。其機制就是調(diào)控張力蛋白同源物（PTEN）和Akt信號途徑。
研究發(fā)現(xiàn)TGF-β1主要負責(zé)上調(diào)腫瘤衍生因子miR-494的表達,。miR-494的表達不僅增強CXCR4介導(dǎo)的MDSC趨化作用,，也改變腫瘤細胞內(nèi)在的凋亡/生存信號，促進MDSCs在腫瘤組織中積累,。
因此,，PTEN的下調(diào)激活A(yù)kt信號途徑能促進腫瘤細胞的浸潤和轉(zhuǎn)移。體內(nèi)實驗中抑制miR-494將大大扭轉(zhuǎn)了MDSCs的活動,，進而抑制腫瘤的生長,。總的來說,，研究結(jié)果表明,，TGF-β1誘導(dǎo)miR-494的表達導(dǎo)致MDSCs在腫瘤組織中積累，這一結(jié)果提示MicroRNA-494可能是一種治療癌癥的潛在新靶標(biāo),。（生物谷：Bioon.com）
doi:10.4049/jimmunol.1103505
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PMID:
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.
