PFKM Promotes the Progression of Gastric Cancer by Up-regulating CNTN1 Expression Through H3K18la Modification

Gastric cancer (GC) stands as one of the most common malignancies globally, characterized by significant incidence rates. Phosphofructokinase muscle isoform (PFKM), a critical rate-limiting enzyme in glycolysis, has its expression modulated by lactate production in tumor cells. The objective of this study is to elucidate the underlying molecular mechanisms by which PFKM contributes to the pathogenesis of GC. The viability, migration, and invasion of GC cells were analyzed by CCK-8 and transwell assays. Each condition was repeated three times. The regulation of H3K18la on transcription activity of CNTNl was evaluated by·dua-luciferase reporter assay. Animal experiment was performed using nude mice with six mice in each group, and tumor growth was evaluated. Statistical analysis was performed using GraphPad Prism software with t-test, one-way or two-way ANOVA. We found that PFKM was over-expressed in GC. Downregulated PFKM restrained the viability, migration, invasion, glucose uptake, and lactate production of GC cells. Mechanically, PFKM interacted with CNTN1 and facilitated the enrichment of H3K18la at the CNTN1 promoter region. Overexpression of CNTN1 reversed the inhibitory effects of PFKM knockdown on GC progression. Our research showed that increasing PFKM levels accelerated GC development by regulating CNTN1 expression through mechanisms involving histone lactylation, which could potentially contribute to novel approaches in diagnosing and treating GC.