MicroRNA-9 Regulates the Differentiation and Function of Myeloid-Derived Suppressor Cells via Targeting Runx1

被引:74
|
作者
Tian, Jie [1 ,2 ]
Rui, Ke [2 ]
Tang, Xinyi [2 ]
Ma, Jie [2 ]
Wang, Yungang [2 ]
Tian, Xinyu [2 ]
Zhang, Yue [1 ]
Xu, Huaxi [2 ]
Lu, Liwei [3 ]
Wang, Shengjun [1 ,2 ]
机构
[1] Jiangsu Univ, Affiliated Peoples Hosp, Dept Lab Med, Zhenjiang 212002, Peoples R China
[2] Jiangsu Univ, Inst Lab Med, Jiangsu Key Lab Lab Med, Zhenjiang 210013, Peoples R China
[3] Univ Hong Kong, Dept Pathol, Hong Kong 999077, Hong Kong, Peoples R China
来源
JOURNAL OF IMMUNOLOGY | 2015年 / 195卷 / 03期
基金
中国国家自然科学基金;
关键词
ANTITUMOR IMMUNE-RESPONSES; FACTOR CREB; EXPRESSION; RECEPTOR; CANCER; PARTICULATE; PROMOTER; AML1; HEMATOPOIESIS; EXPANSION;
D O I
10.4049/jimmunol.1500209
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1301 / 1311
页数:11
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