YTHDF3-TRIM2-P53 axis promotes malignant progression in uveal melanoma (UVM).

Uveal melanoma (UVM) is a rare malignant tumor originating from uveal melanocytes. It accounts for 3 %-5 % of all melanomas and is the most common intraocular malignancy in adults. Advances in the treatment of UVM rely on a deeper understanding of its unique molecular mechanisms.Differential and survival analyses assessed YTHDF3 expression ...
and prognosis in UVM. CCK8 and colony formation assays evaluated the impact of YTHDF3 on tumor proliferation. Transwell and wound healing assays examined its effect on tumor migration. GEO data identified potential substrates modified by YTHDF3, while RIP-qPCR confirmed m6A modification. Animal models validated the tumor-promoting role of YTHDF3.Bioinformatics analysis shows that high expression of YTHDF3 is associated with poor prognosis in UVM. Functional analysis showed that YTHDF3 promoted tumor proliferation, invasion, and migration. RIP-qPCR confirmed that TRIM2 is an m6A modification substrate of YTHDF3. CoIP experiments confirmed the interaction between TRIM2 and P53. Cycloheximide (CHX) pulse-chase assay demonstrated that TRIM2 degraded P53 protein through ubiquitination. Animal models verified that TRIM2 knockdown could inhibit the tumor-promoting effect of YTHDF3.In this study, our findings show that TRIM2 acts as an m6A-modified substrate of YTHDF3, promoting P53 protein degradation through the ubiquitin-proteasome system. Notably, silencing TRIM2 effectively reduced the tumorigenic effects of YTHDF3 in UVM.
Mesh Terms:
Animals, Cell Line, Tumor, Cell Movement, Cell Proliferation, Disease Progression, Gene Expression Regulation, Neoplastic, Humans, Male, Melanoma, Mice, Mice, Nude, RNA-Binding Proteins, Tripartite Motif Proteins, Tumor Suppressor Protein p53, Uveal Melanoma, Uveal Neoplasms
Cell Signal
Date: Mar. 01, 2026
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