Targeting of SMYD3 attenuates Uveal Melanoma progression via inhibiting the JAK2/STAT3 signaling pathway

Uveal melanoma (UVM) represents the leading primary malignancy of the eye in adults. UVM derives from melanocytes located in the uvea of the eye and is primarily characterized by choroidal melanoma. SMYD3 is an important tumor progression factor in multiple tumors. The functions of SMYD3 in UVM have not yet been clarified. Our study aims to characterize the functional impacts of SMYD3 in UVM progression. The expression status of SMYD3 in UVM has been investigated in the UVM-related single-cell database and TCGA-UVM database. Colony formation, EdU, Transwell, wound healing, and in vivo experiments were used to analyze the biological functions’ changes after SMYD3 blocking in UVM cell lines. The single-cell database showed that SMYD3 is enriched in malignant cell type, and is associated with an elevated risk of UVM. The TCGA-UVM study discovered that SMYD3 can be an independent prognostic biomarker in UVM. SMYD3 knockdown or inhibition was shown to limit UVM cell proliferation, migration, and invasion in vitro as well as tumor growth in vivo. The mechanistic analysis indicates that SMYD3 influences the development of UVM through the regulation of JAK2/STAT3 signaling pathway. High expression of SMYD3 related to the poor survival status in UVM. Downregulated SMYD3 expression can prevent UVM progression via blocking the JAK2/STAT3 signaling pathway. These results suggest that SMYD3 as an independent biomarker and therapeutic target in UVM.