Myeloid-derived suppressor cells facilitie invasion and metastasis of papillary thyroid cancer cells by repressing miR-486-3p

Background：In present study, we aimed to evaluate the level as well as function of circulating MDSCs in papillary thyroid cancer (PTC), and also explore the underlying mechanism of MDSCs during tumor progression. Methods：microRNA arrays and RNA-seq analysis were conducted to screened out differentially expressed miRNAs and mRNAs between TPC-1 cells cocultured with PMN-MDSCs and untreated TPC-1 cell line. Results：19 miRNAs were differentially expressed, of which 10 were downregulated and 9 were upregulated in MDSC-conditioned cancer cells. GO analysis of miRNA predicted target genes showed that inflammatory related response were enriched. Besides, these genes were mainly related to NF-kappa B, PI3K-AKT and TNF signaling pathways which are associated with immune response as well as cancer development by KEGG pathway analysis. For validation, qRT-PCR was used to assess the differentially expressed miRNA and the trends in the expression was consistent between microRNA-seq and qRT-PCR. Conclusion：Collectively, our work explore the mechanism by which PMN-MDSCs paly a critical role in PTC 6 samples of TPC-1 cells cocultured with PMN-MDSCs and 4 samples of TPC-1 untreated cells were subjected to mirna and mrna profiles

背景：本研究旨在评估甲状腺乳头状癌（papillary thyroid cancer, PTC）患者循环髓系来源抑制细胞（myeloid-derived suppressor cells, MDSCs）的水平与功能，并探究MDSCs在肿瘤进展过程中的潜在作用机制。
方法：本研究通过microRNA芯片与RNA测序（RNA-seq）分析，筛选出与多形核髓系来源抑制细胞（polymorphonuclear myeloid-derived suppressor cells, PMN-MDSCs）共培养的TPC-1细胞与未处理TPC-1细胞系之间的差异表达microRNA（miRNA）与信使RNA（mRNA）。
结果：在经MDSCs条件培养液培养的癌细胞中，共筛选出19个差异表达的miRNA，其中10个表达下调，9个表达上调。对miRNA预测靶基因进行基因本体（Gene Ontology, GO）富集分析显示，炎症相关反应显著富集。通过京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路分析发现，这些靶基因主要与NF-κB、PI3K-AKT及肿瘤坏死因子（tumor necrosis factor, TNF）信号通路相关，上述通路均与免疫应答及肿瘤发生发展密切相关。为验证测序结果，本研究采用实时定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）对差异表达的miRNA进行验证，miRNA测序与qRT-PCR结果的表达趋势一致。
结论：综上，本研究揭示了PMN-MDSCs在甲状腺乳头状癌中发挥关键作用的潜在机制。本研究共纳入6株与PMN-MDSCs共培养的TPC-1细胞样本及4株未处理TPC-1细胞样本，均进行了miRNA与mRNA表达谱检测。