Affiliation:
1. The Affiliated Hospital of Qingdao University
2. Qingdao University
Abstract
Abstract
Background: Choroidal melanoma (CM) accounts for 70% of uveal melanomas and is prone to metastasize and invade. Previous studies have reported that forkhead box protein 3 (FOXP3) is associated with carcinogenesis, however, the effect of FOXP3 on CM remains unclear. The purpose of the study is to explore the role of FOXP3 in the progression of CM and to elucidate its related mechanisms.
Methods: FOXP3 protein expression was detected in CM clinical specimens and CM cells. We then established a cell line with stable FOXP3 knockout as well as a cell line that transiently overexpressed FOXP3, and their transfection efficiencies were detected by Western blotting (WB). The effects of FOXP3 on cell biological functions and epithelial-mesenchymal transition (EMT) in CM were verified via the CCK-8 assay, monoclonal formation assay, migration and invasion assays, WB and tumorigenesis assay in nude mice in vivo. We also demontrated that FOXP3 promoted CM development through the Wnt5a/CaMKII signaling pathway.
Results: The level of FOXP3 was found to be upregulated in CM clinical specimens and CM cells. The overexpression of FOXP3 promoted the proliferation, migration, invasion, and EMT process of CM cells in vitro, while the knockdown of FOXP3 inhibited these cell functions in vitro and tumor growth in vivo. In addition, FOXP3 was found promoting the progression of CM, including EMT, through the Wnt5a/CaMKII signaling pathway.
Conclusion: This study demonstrated that FOXP3 promoted the development of choroidal melanoma through the Wnt5a/CaMKII signaling pathway as an oncogenic factor of CM, and thereby provides a novel potential target for the pathogenesis of CM.
Publisher
Research Square Platform LLC