MicroRNA-9 Regulates the Differentiation and Function of Myeloid-Derived Suppressor Cells via Targeting Runx1
MicroRNA-9 Regulates the Differentiation and Function of Myeloid-Derived Suppressor Cells via Targeting Runx1
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MicroRNA-9通过靶向Runx1调节骨髓源性抑制细胞的分化和功能
DOI：
10.4049/jimmunol.1500209
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发表时间：
2015-08-01
影响因子：
4.4
通讯作者：
Wang, Shengjun
中科院分区：
文献类型：
--
作者：
Tian, Jie;Rui, Ke;Wang, Shengjun
髓系来源的抑制细胞(MDSCs)在肿瘤相关免疫抑制中起关键作用，从而影响癌症的有效免疫治疗。然而，调控MDSCs分化和功能的分子机制仍很不清楚。在本研究中，我们发现抑制microRNA(MiR)-9促进了MDSCs的分化，并显著降低了免疫抑制功能，而miR-9的过度表达显著增强了MDSCs的功能。值得注意的是，miR-9基因的敲除显著削弱了MDSCs的活性，并抑制了小鼠Lewis肺癌的肿瘤生长。此外，miR-9通过靶向矮小相关转录因子1来调控MDSC的分化，该转录因子是调节MDSC分化和功能的重要转录因子。此外，研究发现CREB对MDSCs中miR-9的表达有调节作用。综上所述，我们的发现确定了miR-9在调节MDSCs的分化和功能中的关键作用。
Myeloid-derived suppressor cells (MDSCs) play a critical role in tumor-associated immunosuppression, thus affecting effective immunotherapies for cancers. However, the molecular mechanisms involved in regulating the differentiation and function of MDSCs remain largely unclear. In this study, we found that inhibition of microRNA (miR)-9 promoted the differentiation of MDSCs with significantly reduced immunosuppressive function whereas overexpression of miR-9 markedly enhanced the function of MDSCs. Notably, knockdown of miR-9 significantly impaired the activity of MDSCs and inhibited the tumor growth of Lewis lung carcinoma in mice. Moreover, miR-9 regulated MDSCs differentiation by targeting the runt-related transcription factor 1, an essential transcription factor in regulating MDSC differentiation and function. Furthermore, the CREB was found to regulate miR-9 expression in MDSCs. Taken together, our findings have identified a critical role of miR-9 in regulating the differentiation and function of MDSCs.