SMYD3 Emerges as a Potential Therapeutic Target in Uveal Melanoma

Researchers report that blocking the protein SMYD3 slows the progression of uveal melanoma, the most common primary cancer of the eye in adults, by interfering with the JAK2/STAT3 signaling pathway. The study, published in BMC Ophthalmology, combined analysis of patient databases with laboratory experiments in uveal melanoma cell lines and animal models to characterize the role of this protein, whose function in the disease had not previously been clarified.

Uveal melanoma arises from melanocytes located in the uvea of the eye and is primarily characterized by choroidal melanoma. To investigate SMYD3, the team first examined uveal melanoma-related single-cell databases and the TCGA-UVM database. The single-cell data showed that SMYD3 is enriched in the malignant cell type and is associated with an elevated risk of uveal melanoma. Analysis of the TCGA-UVM cohort further indicated that SMYD3 can serve as an independent prognostic biomarker, with high expression of the protein related to poor survival status in patients.

The researchers then tested what happens when SMYD3 is blocked. Using colony formation, EdU, Transwell, and wound-healing assays in uveal melanoma cell lines, they found that both knockdown and pharmacological inhibition of SMYD3 limited cell proliferation, migration, and invasion in vitro. In vivo experiments likewise showed that blocking SMYD3 restrained tumor growth. These functional assays were designed to measure changes in biological behavior after SMYD3 blocking, and the results consistently pointed to reduced malignant activity when the protein was suppressed.

Mechanistic analysis in the study indicates that SMYD3 influences the development of uveal melanoma through regulation of the JAK2/STAT3 signaling pathway. According to the authors’ conclusions, downregulated SMYD3 expression can prevent uveal melanoma progression by blocking this pathway, suggesting that SMYD3 may act as both an independent biomarker and a therapeutic target in the disease.

The findings are limited to the preclinical and database analyses described in the study: the in vitro results come from cell lines, the in vivo results from animal experiments, and the prognostic findings from database cohorts. The authors note that these results suggest SMYD3 as an independent biomarker and therapeutic target in uveal melanoma, a disease for which the study identifies the protein’s enrichment in malignant cells and its link to patient risk as central observations.

Subject of Research: The role of SMYD3 and the JAK2/STAT3 pathway in uveal melanoma progression

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

Article References: Chen, J., Zhang, L., Chen, Y., & Hu, J. (2026). Targeting of SMYD3 attenuates Uveal Melanoma progression via inhibiting the JAK2/STAT3 signaling pathway. BMC Ophthalmology. https://doi.org/10.1186/s12886-026-05437-w

Image Credits: AI Generated

DOI: 10.1186/s12886-026-05437-w

Keywords: uveal melanoma, SMYD3, JAK2/STAT3 signaling, choroidal melanoma, TCGA-UVM, single-cell analysis, prognostic biomarker, tumor growth, cell migration, therapeutic target, eye cancer, preclinical study