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SPLUNC1 regulates LPS-induced progression of nasopharyngeal carcinoma and proliferation of myeloid-derived suppressor cells

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Abstract

Nasopharyngeal carcinoma (NPC) is one of the aggressive malignant tumors with high mortality, and the proliferation of myeloid-derived suppressor cells (MDSCs) could promote the metastasis of NPC through inhibiting the function of T cells. Meanwhile, SPLUNC1 was known to inhibit the malignant behavior of NPC cells, while the detailed function of SPLUNC1 in LPS-modified immune microenvironment of NPC remains unclear. To assess the impact of SPLUNC1 in immune microenvironment during the progression of NPC, NPC cells were exposed to LPS and then co-cultured with MDSCs for 48 h. RT-qPCR and western blot were performed to evaluate the mRNA and protein level of SPLUNC1, CXCL-2 and CXCR-2, respectively. The level of IL-1β, IL-6, TNF-α, PD-L1, Arg-1 and iNOS were tested by ELISA. Meanwhile, the expression of CD33+ was tested by flow cytometry. The expression of CXCL-2 and CXCR-2 in NPC cells was higher, compared to that in NP69 cells. In contrast, SPLUNC1 level in NPC cells was much lower than that in NP69 cells. SPLUNC1 level was negatively correlated with CXCL-2 and CXCR-2. Overexpression of SPLUNC1 reversed LPS-induced inflammatory responses and proliferation in NPC cells. In addition, SPLUNC1 upregulation could reverse LPS-induced proliferation of MDSCs in tumor microenvironment. Meanwhile, SPLUNC1 overexpression could regulate CXCL-2/CXCR-2 axis through decreasing CXCL-2 and CXCR-2 protein and mRNA expression. SPLUNC1 regulates LPS-induced progression of nasopharyngeal carcinoma and proliferation of MDSCs. Thus, our study might provide a theoretical basis for discovering new strategies against NPC.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (Grant No. 82173201), the Natural Science Foundation of Hunan Province (Grant No. 2021JJ30422), and Hunan Cancer Hospital Climb Plan (Grant No. 2020NSFC-A001). The authors received no financial support for the research, authorship, or publication of this article.

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  1. Ling Tang and Ling Peng contributed equally to this work.

Authors and Affiliations

  1. Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China

    Ling Tang, Ling Peng, Huai Liu, Tengfei Xiao, Wangning Gu, Hongmin Yang, Hui Wang & Pan Chen

  2. Key Laboratory of Translational Radiation Oncology, Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan Province, China

    Ling Tang & Hui Wang

  3. Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China

    Ling Peng

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Contributions

HW and PC put forward to the hypothesis and revised the manuscript. PC wrote this manuscript. LT, LP and HL performed the part of experiment. Data analysis in the study was conducted by TX, WG and HY. All authors read and approved the final manuscript.

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Correspondence to Hui Wang or Pan Chen.

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Tang, L., Peng, L., Liu, H. et al. SPLUNC1 regulates LPS-induced progression of nasopharyngeal carcinoma and proliferation of myeloid-derived suppressor cells. Med Oncol 39, 214 (2022). https://doi.org/10.1007/s12032-022-01816-7

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