Circulating Myeloid-derived Suppressor Cells Facilitate Invasion of Thyroid Cancer Cells by Repressing miR-486-3p
Circulating Myeloid-derived Suppressor Cells Facilitate Invasion of Thyroid Cancer Cells by Repressing miR-486-3p
复制标题
循环骨髓源性抑制细胞通过抑制 miR-486-3p 促进甲状腺癌细胞的侵袭。
DOI：
10.1210/clinem/dgaa344
复制
发表时间：
2020-08-01
影响因子：
5.8
通讯作者：
Xiao, Haipeng
中科院分区：
文献类型：
--
作者：
Chen, Li;Xiong, Li;Xiao, Haipeng
背景：髓源性抑制细胞（Myeloid-derived suppressor cells, MDSCs）越来越被认为是肿瘤发展的推动者。然而，MDSCs在甲状腺乳头状癌（PTC）进展中的作用尚未明确探讨。目的：我们旨在评估PTC中循环MDSCs的水平和功能。方法：采用流式细胞术检测PTC或良性甲状腺结节患者和健康对照者循环多形核(PMN)-MDSCs和单核mdscs的比例。为了进行免疫抑制活性分析，将分选的循环MDSCs与CD3/ cd28共刺激的T淋巴细胞共培养，并测定T细胞的增殖情况。将PTC细胞系（TPC-1和BC-PAP）与PMN-MDSCs共培养，观察其对细胞迁移、侵袭、增殖和凋亡的影响。在与PMN-MDSCs共培养或不与PMN-MDSCs共培养的TPC-1细胞中，研究了微核糖核酸（rna）和信使rna的差异表达及其功能。结果：PTC患者外周血单个核细胞中PMN-MDSCs增多。循环PMN-MDSCs表现出强烈的T细胞抑制活性。PTC细胞在体外和体内与分选的PMN-MDSCs共培养时显示出增强的侵袭能力。PMN-MDSCs降低miR-486-3p和活化核因子kappa B2 （NE-kappa B2）的表达，后者是miR-486-3p的直接靶点。miR-486-3p的挽救减少了PMN-MDSCs诱导的细胞迁移和侵袭。结论：总的来说，我们的工作表明循环PMN-MDSCs促进PTC进展。PMN-MDSCs通过抑制miR-486-3p，促进NF-kappa B2信号通路的活性，从而加速PTC细胞的侵袭，可能为甲状腺癌的治疗提供新的治疗策略。
Background: Myeloid-derived suppressor cells (MDSCs) have become increasingly recognized as facilitators of tumor development. However, the role of MDSCs in papillary thyroid carcinoma (PTC) progression has not been clearly explored.Objective: We aimed to evaluate the levels and function of circulating MDSCs in PTC.Methods: The proportion of circulating polymorphonuclear (PMN)-MDSCs and mononuclearMDSCs from patients with PTC or benign thyroid nodules and healthy controls was measured using flow cytometry. For immunosuppressive activity analysis, sorted circulating MDSCs were cocultured with CD3/CD28-costimulated T lymphocytes and the proliferation of T cells was determined. PTC cell lines (TPC-1 and BC-PAP) were cocultured with PMN-MDSCs, and the effects on cell migration, invasion, proliferation, and apoptosis were evaluated. The differential expressed microribonucleic acids (RNAs) and messenger RNAs and their function were also explored in TPC-1 cells cocultured with or without PMN-MDSCs.Results: PMN-MDSCs were increased in peripheral blood mononuclear cells of patients with PTC. Circulating PMN-MDSCs displayed strong T cell suppressive activity. PTC cells demonstrated enhanced invasive capabilities in vitro and in vivo when cocultured with sorted PMN-MDSCs. PMN-MDSCs decreased expression of miR-486-3p and activated nuclear factor kappa B2 (NE-kappa B2), a direct target of miR-486-3p. Rescue of miR-486-3p diminished the cell migration and invasion induced by PMN-MDSCs.Conclusion: Collectively, our work indicates that circulating PMN-MDSCs promote PTC progression. By suppressing miR-486-3p, PMN-MDSCs promote the activity of the NF-kappa B2 signaling pathway, resulting in accelerated invasion of PTC cells, which may provide new therapeutic strategies for treatment of thyroid cancer.