J Immunol. 2015 Aug 1;195(3):1301-11. doi: 10.4049/jimmunol.1500209. Epub 2015 Jun 19.

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

Tian J1, Rui K2, Tang X2, Ma J2, Wang Y2, Tian X2, Zhang Y3, Xu H2, Lu L4, Wang S5.

Author information

1Department of Laboratory Medicine, Affiliated People’s Hospital, Jiangsu University, Zhenjiang 212002, China; Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang 210013, China; and.2Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang 210013, China; and.3Department of Laboratory Medicine, Affiliated People’s Hospital, Jiangsu University, Zhenjiang 212002, China;4Department of Pathology, University of Hong Kong, Hong Kong 999077, China.5Department of Laboratory Medicine, Affiliated People’s Hospital, Jiangsu University, Zhenjiang 212002, China; Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang 210013, China; and sjwjs@ujs.edu.cn.

Abstract

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.

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