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Long noncoding RNA Pvt1 regulates the immunosuppression activity of granulocytic myeloid-derived suppressor cells in tumor-bearing mice.
Zheng Y1,2, Tian X1,2, Wang T3, Xia X2, Cao F4, Tian J5, Xu P6, Ma J2, Xu H2, Wang S7,8.
Author information
1Department of Laboratory Medicine, the Affiliated People’s Hospital, Jiangsu University, Zhenjiang, 212013, China.2Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.3Department of Laboratory Medicine, the Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi Children’s Hospital, Wuxi, China.4Department of Laboratory Medicine, Zhenjiang Hospital of Chinese Traditional and Western Medicine, Zhenjiang, China.5Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China. tjj850913@163.com.6Department of Laboratory Medicine, The Fifth People’s Hospital of Suzhou, Suzhou, China. 573311485@qq.com.7Department of Laboratory Medicine, the Affiliated People’s Hospital, Jiangsu University, Zhenjiang, 212013, China. sjwjs@ujs.edu.cn.8Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China. sjwjs@ujs.edu.cn.
Abstract
BACKGROUND:
Myeloid-derived suppressor cells (MDSCs) participate in tumor-elicited immunosuppression by dramatically blocking T-cell-induced antitumor responses, thereby influencing the effectiveness of cancer immunotherapies. Treatments that alter the differentiation and function of MDSCs can partially restore antitumor immune responses. The long noncoding RNA plasmacytoma variant translocation 1 (lncRNA Pvt1) is a potential oncogene in a variety of cancer types. However, whether lncRNA Pvt1 is involved in the regulation of MDSCs has not been thoroughly elucidated to date.
METHODS:
MDSCs or granulocytic MDSCs (G-MDSCs) were isolated by microbeads and flow cytometry. Bone marrow derived G-MDSCs were induced by IL-6 and GM-CSF. The expression of lncRNA Pvt1 was measured by qRT-PCR. Specific siRNA was used to knockdown the expression of lncRNA Pvt1 in G-MDSCs.
RESULTS:
In this study, we found that knockdown of lncRNA Pvt1 significantly inhibited the immunosuppressive function of G-MDSCs in vitro. Additionally, lncRNA Pvt1 knockdown reduced the ability of G-MDSCs to delay tumor progression in tumor-bearing mice in vivo. Notably, lncRNA Pvt1 was upregulated by HIF-1α under hypoxia in G-MDSCs.
CONCLUSIONS:
Taken together, our results demonstrate a critical role for lncRNA Pvt1 in regulating the immunosuppression activity of G-MDSCs, and lncRNA Pvt1 might thus be a potential antitumor immunotherapy target.
KEYWORDS:
Immunosuppression; Long noncoding RNA; Myeloid-derived suppressor cells; Pvt1