Study on miR-144-3p targeting CDH11 to suppress malignant biological behaviors of gastric cancer

Objective : miR-144-3p is a tumor suppressor in gastric cancer, however, the mechanisms by which it inhibits gastric cancer invasion and metastasis have not been fully elucidated. This study aimed to determine whether miR-144-3p suppresses epithelial–mesenchymal transition (EMT) and tumor metastasis by targeting the cell adhesion molecule CDH11, thereby providing a novel molecular target for the intervention of gastric cancer metastasis. Methods : Colony formation, cell cycle analysis, wound-healing, and Transwell assays were performed to evaluate the effects of miR-144-3p and CDH11 on gastric cancer cell proliferation, cell cycle progression, migration, and invasion. Subcutaneous xenograft and lung metastasis models in nude mice were established to assess tumorigenicity and distant colonization in vivo. Dual-luciferase reporter assays and quantitative PCR were used to validate the targeting relationship between miR-144-3p and CDH11. Rescue experiments using wound-healing and Transwell assays were conducted to further confirm the reversal effects of CDH11 overexpression on miR-144-3p function, and Western blotting was performed to analyze changes in EMT-related protein expression. Results : Overexpression of miR-144-3p significantly inhibited gastric cancer cell proliferation, migration, invasion, and the growth of subcutaneous xenografts and lung metastases both in vitro and in vivo, accompanied by suppression of EMT. Dual-luciferase reporter assays demonstrated that miR-144-3p directly targets and negatively regulates CDH11. Silencing of CDH11 similarly suppressed gastric cancer cell proliferation, migration, invasion, and tumor growth in both subcutaneous and pulmonary metastasis models, while inhibiting EMT. Rescue experiments confirmed that CDH11 overexpression partially reversed the inhibitory effects of miR-144-3p on gastric cancer cell migration and invasion and restored the miR-144-3p–induced EMT phenotype. Conclusion : The miR-144-3p/CDH11 axis may serve as a potential diagnostic biomarker and therapeutic target for gastric cancer.