Journal
JOURNAL OF IMMUNOLOGY
Volume 200, Issue 8, Pages 2603-2614Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1701721
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Funding
- National Natural Science Foundation of China [91029736, 9162910, 81600436, 91442111]
- Joint NSFC-ISF Research Program - National Natural Science Foundation of China [31461143010]
- Joint NSFC-ISF Research Program - Israel Science Foundation [31461143010]
- Ministry of Science and Technology grant (863 program) [2008AA02Z129]
- National Key Research and Development Program of China [2016YFC1303604]
- Program for Changjiang Scholars and Innovative Research Team in University (Ministry of Education of China) [IRT13023]
- State Key Laboratory of Medicinal Chemical Biology
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Myeloid-derived suppressor cells (MDSCs) are major regulators of immune responses in cancer. Both C/EBP homologous protein (CHOP) and C/EBP beta play a critical role in regulating immunosuppressive function of MDSCs. In this study, we identified a novel long noncoding RNA termed as lnc-chop in MDSCs, which may interact with CHOP and the C/EBP beta isoform liver-enriched inhibitory protein. The binding of lnc-chop with both CHOP and the C/EBP beta isoform liver-enriched inhibitory protein promoted the activation of C/EBP beta and upregulated the expression of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2, which are related to the immunosuppressive function of MDSCs in inflammatory and tumor environments. Additionally, lnc-chop also promoted the enrichment of H3K4me3 on the promoter region of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2. These findings suggest an important role of lnc-chop in controlling immunosuppressive function of MDSCs in the tumor environment.
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