Promotion of human choroidal melanoma cell metastases by FOXP3 via Wnt5a/CaMKII signaling pathway.

Aim: To investigate the role of Forkhead box protein P3 (FOXP3) in choroidal melanoma (CM) metastases and elucidate its underlying mechanisms.

Methods: FOXP3 protein expression was analyzed in CM clinical specimens and cell lines. A stable FOXP3 knockout cell line and a transient FOXP3-overexpressing cell line were established, with transfection efficiencies confirmed by Western blotting (WB). Functional assays, including monoclonal formation, cell counting kit-8 (CCK-8) proliferation, migration, invasion, and in vivo tumorigenesis assays in nude mice, were performed to assess the biological effects of FOXP3. Additionally, WB was employed to evaluate epithelial-mesenchymal transition (EMT) markers and the activation of the Wnt5a/CaMKII signaling pathway.

Results: FOXP3 expression was significantly elevated in both CM clinical specimens and cell lines. Functional analyses revealed that FOXP3 enhanced CM cell proliferation, migration, and invasion in vitro and promoted tumorigenesis in vivo. Mechanistically, FOXP3 upregulated EMT-related proteins and activated the Wnt5a/CaMKII signaling pathway. Rescue experiments further confirmed that the oncogenic effects of FOXP3 were mediated via modulation of the Wnt5a/CaMKII axis.

Conclusion: This study identifies FOXP3 as an oncogenic driver in CM, promoting tumor progression through the Wnt5a/CaMKII signaling pathway. These findings provide new insights into the molecular mechanisms of CM pathogenesis and highlight FOXP3 as a potential therapeutic target.