FTO Upregulates GLG1 Expression via m⁶A Methylation Modification to Facilitate Gastric Cancer Cell Migration and...

Due to the rapid progression and metastatic nature of gastric cancer (GC), the advanced diagnosis and poor prognosis of GC remain a great clinical challenge despite advances in treatment. Fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m⁶A) demethylase, participates in GC development in an m⁶A methylation modification-related way. This study aimed to identify GC-related factors that could be regulated by FTO and golgi glycoprotein 1 (GLG1) was found due to its significant upregulation in GC and correlation with advanced stages and lymph node metastases. GLG1's expression was strongly linked to poor overall survival, disease-specific survival, and progression-free interval. Further, GLG1 was implicated in GC metastasis and invasion, showing increased expression in invasive GC types. GLG1 levels were elevated in GC samples and cell lines, especially in metastatic contexts. Knockdown experiments in vitro and in vivo demonstrated GLG1's role in promoting GC aggressiveness and metastasis. FTO, an m⁶A modifying enzyme, was found to positively regulate GLG1, affecting GC cell phenotypes through mRNA stability modulation. Knockdown of FTO decreased GLG1 expression and mitigated GC cell aggressiveness, indicating a regulatory mechanism involving m⁶A modification and highlighting the potential therapeutic targets in GLG1 and FTO for GC treatment. In conclusion, the modulatory effect of FTO upon GLG1 expression via m⁶A methylation modification reveals a new layer of post-transcriptional modulation that contributes to the aggressive phenotype of GC cells. This study elucidates the dynamic interaction between GLG1 and FTO in influencing GC cell behavior and positions these molecules as potential targets for therapeutic strategies aimed at mitigating GC progression and metastasis.