CircFoxo3 knockdown inhibit gastric cancer progression by regulating Foxo3.

Improving the diagnosis and treatment of gastric cancer is a significant challenge worldwide. Circular RNAs (circRNAs), a recently identified class of endogenous non-coding RNAs with covalently closed-loop structures, have emerged as key regulators in tumorigenesis. CircFoxo3 has been studied in various cancer types, while its functional role in GC remains poorly understood. In this study, we found that circFoxo3 is significantly upregulated in GC tissues and cell lines compared to paired normal controls. Functional analyses demonstrated that knockdown of circFoxo3 markedly inhibited GC cell proliferation and migration, whereas overexpression of circFoxo3 produced the opposite effects. Mechanistically, circFoxo3 knockdown reduced forkhead box (Fox) transcription factors FOXO3 mRNA and protein levels. FOXO3a is involved in regulating cancer cell proliferation. Bioinformatic analysis revealed high expression of FOXO3 in GC tumor samples, a finding confirmed in both GC tissues and cell lines. A tumor xenograft model was used to examine the effect of circFoxo3 on tumor growth in vivo. The low circFoxo3 expression reduced the volume of the tumor and decreased its proliferation. Collectively, our findings identify circFoxo3 as an oncogenic factor in GC progression.