Gastric cancer is a kind of malignant tumor that seriously endangers human life and health. Its incidence rate and mortality rate are among the highest in the global malignant tumors. Therefore, this study explored the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in the progression of gastric cancer and its underlying mechanism. Patients with gastric cancer were collected, and human GC cell lines (stomach gastric carcinoma 7901, stomach gastric carcinoma 823 , human gastric carcinoma cell line 803 and adenocarcinoma gastric stomach) were used in this study. We utilized glucose consumption, cell migration, and ELISA assay kits to investigate the function of GC. To understand its mechanism, we employed quantitative PCR (qPCR), western blot, and m6A methylated RNA immunoprecipitation assay. FKFB3 protein expression levels in patients with gastric cancer were increased. The induction of PFKFB3 mRNA expression levels in patients with gastric cancer or gastric cancer cell lines. Gastric cancer patients with high PFKFB3 expression had a lower survival rate. PFKFB3 high expression possessed the probability of pathological stage, lymph node metastasis or distant metastasis in patients with gastric cancer. PFKFB3 upregulation promoted cancer progression and Warburg effect progression of gastric cancer. PFKFB3 upregulation reduced pyroptosis and suppressed nucleotidebinding domain, leucinerich repeat containing protein 3-induced pyroptosis of gastric cancer. M6A-forming enzyme methyltransferase-like 3 increased PFKFB3 stability. Taken together, the M6A-forming enzyme methyltransferase-like 3 increased PFKFB3 stability and reduced pyroptosis in the model of gastric cancer through the Warburg effect. The PFKFB3 gene represents a potential therapeutic strategy for the treatment of gastric cancer.

中文翻译：

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FKFB3 的 M6A 甲基化通过 NLRP3 减少胃癌的焦亡。

胃癌是一种严重危害人类生命健康的恶性肿瘤。其发病率和死亡率均位居全球恶性肿瘤之首。因此，本研究探讨6-磷酸果糖2-激酶/果糖-2,6-双磷酸酶3（PFKFB3）在胃癌进展中的作用及其潜在机制。本研究收集胃癌患者，使用人GC细胞系（胃癌7901、胃癌823、人胃癌细胞系803和胃腺癌）。我们利用葡萄糖消耗、细胞迁移和 ELISA 检测试剂盒来研究 GC 的功能。为了了解其机制，我们采用了定量 PCR (qPCR)、蛋白质印迹和 m6A 甲基化 RNA 免疫沉淀测定。胃癌患者中FKFB3蛋白表达水平升高。胃癌患者或胃癌细胞系中 PFKFB3 mRNA 表达水平的诱导。PFKFB3高表达的胃癌患者生存率较低。PFKFB3高表达具有胃癌患者病理分期、淋巴结转移或远处转移的可能性。PFKFB3上调促进癌症进展和胃癌的Warburg效应进展。PFKFB3 上调可减少焦亡并抑制核苷酸结合域、含有蛋白 3 的富含亮氨酸重复序列诱导的胃癌焦亡。M6A 形成酶甲基转移酶样 3 增加了 PFKFB3 的稳定性。综上所述，M6A 形成酶甲基转移酶样 3 通过 Warburg 效应增加了 PFKFB3 的稳定性并减少了胃癌模型中的细胞焦亡。PFKFB3基因代表了治疗胃癌的潜在治疗策略。