miRNA-4722-3p Targets GGT5 and Inhibits Gastric Cancer Cell Progression via the PI3K/AKT-MAPK-MMPs Signaling Pathway

Gastric cancer (GC) is a common gastrointestinal malignancy, with more than one million new cases diagnosed each year. Identifying biomarkers for early diagnosis and prognosis is crucial to improving clinical outcomes. However, existing biomarkers lack sufficient sensitivity and specificity. Gamma-glutamyltransferases (GGTs) are a family of enzymes involved in glutathione metabolism and cancer progression, and recent studies have suggested their potential as tumor markers. Among them, GGT5 (Gamma-glutamyltransferase 5) has been reported to play oncogenic roles in gastrointestinal cancers.This study aims to explore the regulatory relationship between miRNA-4722-3p and GGT5 and its impact on GC progression, evaluating the potential of miRNA-4722-3p as a diagnostic biomarker for GC. Bioinformatics tools, including TargetScan, miRWalk, and miRDB, were used to predict miRNAs that bind to the 3’ untranslated region (UTR) of GGT5. miRNA-4722-3p was selected due to its lowest binding free energy and was validated through dual-luciferase reporter assays. RT-qPCR and Western blotting confirmed that miRNA-4722-3p directly targets and inhibits GGT5 expression in GC cells. Functional assays demonstrated that miRNA-4722-3p upregulation significantly suppressed GC cell proliferation and migration, whereas its downregulation enhanced these processes. Furthermore, miRNA-4722-3p inhibited GGT5 expression through the PI3K/AKT-MAPK-MMPs signaling pathway, reinforcing its suppressive effects. Overall, miRNA-4722-3p and GGT5 may serve as promising biomarkers for the early diagnosis and targeted therapy of gastric cancer. Bioinformatics and experiments identify miR-4722-3p as a gastric cancer biomarker. It suppresses tumor growth/metastasis by targeting oncogene GGT5 and inhibiting the PI3K/AKT-MAPK-MMPs pathway, revealing its tumor-suppressive role and offering a novel therapeutic target.