Arginase 2 Promotes Colorectal Cancer Metastasis via PI3K/AKT Pathway Activation and Regulates Tumor Immune Infiltration

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with metabolic reprogramming involved in its pathogenesis. Aberrant Arginase 2 (ARG2) expression is linked to malignant progression, but its role in CRC remains unclear. METHODS: ARG2 expression in CRC and adjacent tissues was analyzed. In vitro experiments were performed after ARG2 knockdown. Mechanistic investigations focused on epithelial-mesenchymal transition (EMT), PI3K/AKT pathway, immune infiltration, and drug sensitivity. RESULTS: ARG2 was upregulated in CRC tissues, correlating with poor prognosis. ARG2 knockdown inhibited CRC cell proliferation, migration, and invasion by reducing Zinc Finger E-Box Binding Homeobox 1 (ZEB1), N-cadherin, and MMP2, suppressing EMT. Additionally, ARG2 knockdown significantly inhibited the PI3K/AKT signaling pathway. Immune infiltration analysis revealed high ARG2 expression correlated with reduced activated B cells and macrophages. Drug sensitivity analysis indicated that high ARG2 expression was associated with decreased efficacy of certain chemotherapeutic agents. CONCLUSION: ARG2 is an independent prognostic marker for CRC. It promotes CRC progression via regulating EMT and PI3K/AKT, holding potential as a novel diagnostic and therapeutic target.