滴虫螺旋体肌肉幼虫排泄分泌物（ML-ESPs）是具有抗肿瘤活性的复杂蛋白质组合。我们先前已证明ML-ESPs抑制A549非小细胞肺癌（NSCLC）细胞系的增殖。然而，ML-ESPs对A549细胞的作用机制，尤其是在转录水平上仍然未知。在本研究中，我们系统地研究了A549细胞在ML-ESPs处理下的全局转录反应的生物信息学分析。然后，我们进一步探究了ML-ESPs对A549细胞中与葡萄糖代谢相关的基因的转录调控。结果显示，ML-ESPs改变了2,860个基因的表达（其中1,634个上调，1,226个下调）。GO和KEGG分析表明，差异表达基因主要与癌症和代谢过程的途径相关。代谢过程的下调基因相互作用网络主要与葡萄糖代谢有关。此外，磷酸果糖激酶（PFKM）、磷酸果糖激酶（PFKL）、2-烯醇化酶（ENO2）、乳酸脱氢酶B（LDHB）、6-磷酸葡萄糖内酯酶（6PGL）、鲁波 糖磷酸-3-上消旋酶（PRE）、转酮酸激酶（TKT）、转醛酶1（TALDO1）这些基因主要参与糖酵解和磷酸戊糖途径（PPP）的调节，均受到ML-ESPs的抑制。有趣的是，与三羧酸循环（TCA）相关的基因，如丙酮酸脱氢酶磷酸酶1（PDP1）、PDP2、顺丁烯二酸水合酶1（ACO1）和α-酮戊二酸脱氢酶（OGDH），则被ML-ESPs上调。总之，ML-ESPs显著改变了A549细胞的转录组谱。我们也为ML-ESPs如何诱导A549细胞中与葡萄糖代谢相关的基因的转录重编程提供了新的见解。版权所有©2023年王、朱、李、潘、李、郭、谢和杜。

Trichinella spiralis (T. spiralis) muscle-larva excretory/secretory products (ML-ESPs) is a complex array of proteins with antitumor activity. We previously demonstrated that ML-ESPs inhibit the proliferation of A549 non-small cell lung cancer (NSCLC) cell line. However, the mechanism of ML-ESPs against A549 cells, especially on the transcriptional level, remains unknow. In this study, we systematically investigated a global profile bioinformatics analysis of transcriptional response of A549 cells treated with ML-ESPs. And then, we further explored the transcriptional regulation of genes related to glucose metabolism in A549 cells by ML-ESPs. The results showed that ML-ESPs altered the expression of 2,860 genes (1,634 upregulated and 1,226 downregulated). GO and KEGG analysis demonstrated that differentially expressed genes (DEGs) were mainly associated with pathway in cancer and metabolic process. The downregulated genes interaction network of metabolic process is mainly associated with glucose metabolism. Furthermore, the expression of phosphofructokinase muscle (PFKM), phosphofructokinase liver (PFKL), enolase 2 (ENO2), lactate dehydrogenase B (LDHB), 6-phosphogluconolactonase (6PGL), ribulose-phosphate-3-epimerase (PRE), transketolase (TKT), transaldolase 1 (TALDO1), which genes mainly regulate glycolysis and pentose phosphate pathway (PPP), were suppressed by ML-ESPs. Interestingly, tricarboxylic acid cycle (TCA)-related genes, such as pyruvate dehydrogenase phosphatase 1 (PDP1), PDP2, aconitate hydratase 1 (ACO1) and oxoglutarate dehydrogenase (OGDH) were upregulated by ML-ESPs. In summary, the transcriptome profiling of A549 cells were significantly altered by ML-ESPs. And we also provide new insight into how ML-ESPs induced a transcriptional reprogramming of glucose metabolism-related genes in A549 cells.Copyright © 2023 Wang, Zhu, Li, Pan, Li, Guo, Xie and Du.