Objective To elucidate the mechanism by which the BANCR/miR-145-5p axis regulates the AKT-GLUT1/HK2 pathway through downstream targets Reg3A/DMBT1 to facilitate the Warburg effect in gastric cancer.

Methods Expression levels of BANCR, miR-145-5p, Reg3A, and DMBT1 were detected by RT-qPCR and Western blot in gastric cancer tissues and cell lines. Dual-luciferase reporter assays confirmed targeted relationships. Glycolytic capacity was assessed via glucose uptake. Immunohistochemistry analyzed molecular expression in 60 paired clinical samples. The prognostic values of key molecules in the BANCR/miR-145-5p-Reg3A/DMBT1 axis were evaluated by Kaplan-Meier survival analysis and Cox proportional hazards regression model.

Results BANCR was significantly upregulated, whereas miR-145-5p was downregulated in gastric cancer tissues, correlating with advanced TNM stage, lymph node metastasis, and poor differentiation. Reg3A and DMBT1 were identified as direct targets of miR-145-5p. Knockdown of BANCR or overexpression of miR-145-5p significantly suppressed Reg3A/DMBT1 expression, reduced AKT phosphorylation and GLUT1/HK2 levels, and inhibited glycolysis. Clinical analysis revealed positive correlations between Reg3A/DMBT1 expression and glycolytic markers, with both serving as independent risk factors for poor prognosis.

Conclusion The BANCR/miR-145-5p axis activates the AKT pathway by targeting Reg3A/DMBT1, thereby promoting GLUT1/HK2/LDHA-mediated glycolysis and facilitating the Warburg effect in gastric cancer. This regulatory axis represents a potential therapeutic target and prognostic biomarker.