NME4, also designated nm23-H4 or NDPK-D, has been known for years for its well-established roles in the synthesis of nucleoside triphosphates, though; little has been known regarding the differential metabolites involved as well as the biological roles NME4 plays in proliferation and invasion of esophageal squamous cell carcinoma (ESCC) cells. To understand the biological roles of NME4 in ESCC cells, lentiviral-based short hairpin RNA interference (shRNA) vectors were constructed and used to stably knock down NME4. Then, the proliferative and invasive variations were assessed using MTT, Colony formation and Transwell assays. To understand the metabolites involved after silencing of NME4 in ESCC cells, widely targeted metabolomic screening was taken. It was discovered that silencing of NME4 can profoundly suppress the proliferation and invasion in ESCC cells in vitro. Metabolically, a total of 11 differential metabolites were screened. KEGG analyses revealed that Tryptophan, Riboflavin, Purine, Nicotinate, lysine degradation, and Linoleic acid metabolism were also involved in addition to the well-established nucleotides metabolism. Some of these differential metabolites, say, 2-Picolinic Acid, Nicotinic Acid and Pipecolinic Acid were suggested to be associated with tumor immunomodulation. The data we described here support the idea that metabolisms occurred in mitochondrial was closely related to tumor immunity.

NME4，也称为nm23-H4或NDPK-D，由于其在三磷酸核苷合成中的公认作用而闻名多年。关于所涉及的差异代谢物以及NME4在食管鳞状细胞癌（ESCC）细胞的增殖和侵袭中所起的生物学作用，人们知之甚少。为了了解NME4在ESCC细胞中的生物学作用，构建了基于慢病毒的短发夹RNA干扰（shRNA）载体，并用于稳定敲低NME4。然后，使用MTT，菌落形成和Transwell分析评估增殖和侵袭性变异。为了了解ESME细胞中NME4沉默后涉及的代谢物，进行了广泛靶向的代谢组学筛选。已经发现沉默NME4可以在体外显着抑制ESCC细胞的增殖和侵袭。代谢上，共筛选了11种差异代谢物。KEGG分析显示，色氨酸，核黄素，嘌呤，烟酸酯，赖氨酸降解和亚油酸代谢除已建立的核苷酸代谢外，也涉及在内。这些差异代谢物中的一些，例如2-吡啶甲酸，烟酸和哌啉酸被认为与肿瘤免疫调节有关。我们在此描述的数据支持线粒体中发生的代谢与肿瘤免疫密切相关的想法。亚油酸和亚油酸的代谢也与成熟的核苷酸代谢有关。这些差异代谢物中的一些，例如2-吡啶甲酸，烟酸和哌啉酸被认为与肿瘤免疫调节有关。我们在此描述的数据支持线粒体中发生的代谢与肿瘤免疫密切相关的想法。亚油酸和亚油酸的代谢也与成熟的核苷酸代谢有关。这些差异代谢物中的一些，例如2-吡啶甲酸，烟酸和哌啉酸被认为与肿瘤免疫调节有关。我们在此描述的数据支持线粒体中发生的代谢与肿瘤免疫密切相关的想法。