Wang Haoxuan, Zhu Yingying, Li Meichen, Pan Jingdan, Li Dan, Guo Wen-Ping, Xie Guangcheng, Du Luanying
Department of Pathogenic Biology, Chengde Medical University, Chengde, Hebei, China.
Department of Clinical Laboratory, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China.
Front Vet Sci. 2023 Jul 31;10:1208538. doi: 10.3389/fvets.2023.1208538. eCollection 2023.
() 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.
（）肌肉幼虫排泄/分泌产物（ML-ESPs）是一组具有抗肿瘤活性的复杂蛋白质。我们之前证明ML-ESPs可抑制A549非小细胞肺癌（NSCLC）细胞系的增殖。然而，ML-ESPs作用于A549细胞的机制，尤其是转录水平的机制，仍不清楚。在本研究中，我们系统地研究了用ML-ESPs处理的A549细胞转录反应的全基因组生物信息学分析。然后，我们进一步探讨了ML-ESPs对A549细胞中与葡萄糖代谢相关基因的转录调控。结果显示，ML-ESPs改变了2860个基因的表达（1634个上调，1226个下调）。GO和KEGG分析表明，差异表达基因（DEGs）主要与癌症通路和代谢过程相关。代谢过程中下调基因的相互作用网络主要与葡萄糖代谢相关。此外，主要调节糖酵解和磷酸戊糖途径（PPP）的磷酸果糖激酶肌肉型（PFKM）、磷酸果糖激酶肝脏型（PFKL）、烯醇化酶2（ENO2）、乳酸脱氢酶B（LDHB）、6-磷酸葡糖酸内酯酶（6PGL）、核糖磷酸-3-表异构酶（PRE）、转酮醇酶（TKT）、转醛醇酶1（TALDO1）的表达被ML-ESPs抑制。有趣的是，三羧酸循环（TCA）相关基因，如丙酮酸脱氢酶磷酸酶1（PDP1）、PDP2、乌头酸水合酶1（ACO1）和氧代戊二酸脱氢酶（OGDH）被ML-ESPs上调。总之，ML-ESPs显著改变了A549细胞的转录组图谱。我们还为ML-ESPs如何诱导A549细胞中葡萄糖代谢相关基因的转录重编程提供了新的见解。
