CONCLUSION: These findings reveal a novel miR-27a-5p–GFPT2–HBP axis that links metabolic reprogramming to Wnt signaling in CRC by suppressing β-catenin activity through the reduction of UDP-GlcNAc-dependent O-GlcNAcylation, thereby restraining CRC progression. The gene discussed is GFPT2; the disease is colorectal carcinoma.