Background: Detecting and treating stomach cancer requires a comprehensive understanding of how gastric cancer develops and progresses. In this context, efforts have been made to elucidate the regulation of glutamine-fructose-6-phosphate transaminase 1 (GFPT1) and Lysine demethylase 4C (KDM4C) in gastric cancer.
Methods: Bioinformatics was utilized to predict the levels and correlation of GFPT1 and KDM4C in gastric cancer, followed by determining their expressions via quantitative real-time polymerase chain reaction (qRT-PCR). The viability (assessed through Cell Counting Kit-8 (CCK-8) assay), proliferation (via colony-forming assay), migration, and invasion (utilizing transwell assay), as well as vasculogenic mimicry (examined through Tube formation assay), in gastric cancer cells, were quantified. Additionally, quantification of GFPT1 and proliferation/epithelial-mesenchymal transition (EMT)-related proteins was conducted through Western blot analysis.
Results: In gastric cancer cells, GFPT1 was found to be abundantly expressed. Overexpression of GFPT1 resulted in increased viability, proliferation, migration, invasion, vasculogenic mimicry, and EMT of gastric cancer cells, while knockdown of GFPT1 had the opposite effects. Moreover, there was a positive correlation between KDM4C and GFPT1 in gastric cancer. Overexpression of KDM4C led to increased expression of GFPT1 and enhanced the aforementioned effects of GFPT1 overexpression, whereas knockdown of KDM4C produced inverse effects. Interestingly, the effects of KDM4C overexpression combined with GFPT1 knockdown, or GFPT1 overexpression combined with KDM4C knockdown, could mutually reverse their effects on the aforementioned cell phenotypes.
Conclusion: KDM4C positively regulates GFPT1, thereby promoting gastric cancer progression. This discovery provides a new avenue for slowing down the progression of gastric cancer.
Keywords: Lysine demethylase 4C; epithelial-mesenchymal transition; gastric cancer; glutamine-fructose-6-phosphate transaminase 1; vasculogenic mimicry.