Abstract
BackgroundRUNX1 overlapping RNA (RUNXOR) is a long non-coding RNA that has been indicated as a key regulator in the development of myeloid cells by targeting runt-related transcription factor 1 (RUNX1). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells consisting of immature granulocytes and monocytes with immunosuppression. However, the impact of lncRNA RUNXOR on the development of MDSCs remains unknown.MethodsBoth the expressions of RUNXOR and RUNX1 in the peripheral blood were measured by qRT-PCR. Human MDSCs used in this study were isolated from tumor tissue of patients with lung cancer by FCM or induced from PBMCs of healthy donors with IL-1β + GM-CSF. Specific siRNA was used to knockdown the expression of RUNXOR in MDSCs.ResultsIn this study, we found that the lncRNA RUNXOR was upregulated in the peripheral blood of lung cancer patients. In addition, as a target gene of RUNXOR, the expression of RUNX1 was downregulated in lung cancer patients. Finally, the expression of RUNXOR was higher in MDSCs isolated from the tumor tissues of lung cancer patients compared with cells from adjacent tissue. In addition, RUNXOR knockdown decreased Arg1 expression in MDSCs.ConclusionsBased on our findings, it is illustrated that RUNXOR is significantly associated with the immunosuppression induced by MDSCs in lung cancer patients and may be a target of anti-tumor therapy.
Highlights
Runtrelated transcription factor 1 (RUNX1) overlapping RNA (RUNXOR) is a long non-coding RNA that has been indicated as a key regulator in the development of myeloid cells by targeting runt-related transcription factor 1 (RUNX1)
The proportion of Myeloidderived suppressor cells (MDSCs) is negatively correlated with the percentage of T helper 1 (Th1)/Cytotoxic T lymphocyte (CTL) cells in the peripheral blood of lung cancer patients MDSCs are a population of cells that accumulate during the progression of various cancers
The phenotype of MDSCs is CD11b + CD33 + HLA-DR-CD14-. These cells inhibit the anti-tumor immune response via different mechanisms: MDSCs produce suppressive molecules, such as Arginase 1 (Arg1), ROS or iNOS, to directly suppress the anti-tumor immune response induced by Th1/CTL cells and promote tumor progression; MDSCs can promote the production of IL-10 to inhibit the CTL response by inducing Tregs or developing into tumor-associated macrophages (TAMs) [10, 22,23,24,25]
Summary
RUNX1 overlapping RNA (RUNXOR) is a long non-coding RNA that has been indicated as a key regulator in the development of myeloid cells by targeting runt-related transcription factor 1 (RUNX1). Myeloidderived suppressor cells (MDSCs) are a heterogeneous population of cells consisting of immature granulocytes and monocytes with immunosuppression. Despite the development of chemotherapy and the integration of targeted therapy aimed at lung cancer, the overall outcomes are still not ideal [1]. The immunosuppression induced by myeloid-derived suppressor cells (MDSCs) has been demonstrated to be a main cause of tumor escape in anti-tumor therapies targeting lung cancer [4,5,6]. MDSCs are a heterogeneous population of immature myeloid cells consisting of precursors for granulocytes, macrophages or dendritic cells (DCs), which accumulate during tumor progression [7, 8]. MDSCs inhibit the anti-tumor immune responses induced by CD4+ T cells, CD8+ T cells and NK cells by releasing Arg, ROS and iNOS.
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