Circular RNA Circ_0079226 Plays an Oncogenic Role in Gastric Cancer via the miR-155-5p/FOXK1/AKT Pathway.

Abstract

Background: Circular RNA (circRNA) is implicated in various biological processes, including the progression of gastric cancer (GC). The specific functions and underlying mechanisms of circ_0079226 in GC are unknown. Methods: We examined cancerous and adjacent noncancerous tissues from 25 patients with GC to evaluate circ_0079226, miR-155-5p, and forkhead transcription factor K1 (FOXK1) expression. Pearson's correlation analysis was used to assess the relationships among these RNAs. We examined their functional roles utilizing in vitro (cell cytotoxicity kit-8, wound healing, and Transwell invasion assays) and in vivo (xenograft mouse models) approaches. Molecular mechanisms were investigated using bioinformatics, dual-luciferase reporter assays, and rescue experiments, while quantitative real-time PCR, western blot, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and protein immunofluorescence (IF) were used to detect gene expression. Results: We found that circ_0079226 and FOXK1 levels were elevated, while miR-155-5p was reduced in GC tissues and cells. An inverse correlation existed between FOXK1 and miR-155-5p, while a direct correlation was observed between FOXK1 and circ_0079226. Circ_0079226 facilitated GC cell proliferation, migration, invasion, and in vivo tumor growth. It functions by sequestering miR-155-5p, which directly targets FOXK1. High miR-155-5p expression mitigated the effects of circ_0079226 on GC cells, and the reintroduction of FOXK1 reversed the inhibitory effects of miR-155-5p. Circ_0079226 boosts FOXK1 and its associated downstream signaling pathways, including FAK, AKT, and p-AKT, through competitive binding with miR-155-5p. Conclusions: In conclusion, circ_0079226 is implicated in GC cell proliferation and metastasis by modulating the miR-155-5p/FOXK1/AKT pathway, presenting it as a potential therapeutic target.