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

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults, accounting for 3-5% of all melanomas.
• Understanding the molecular mechanisms driving UVM is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of YTHDF3 in uveal melanoma.
• To identify molecular targets and pathways regulated by YTHDF3 in UVM.

Main Methods:

• Differential and survival analyses of YTHDF3 expression in UVM.
• In vitro assays (CCK8, colony formation, Transwell, wound healing) to assess proliferation and migration.
• RIP-qPCR and CoIP to confirm m6A modification and protein interactions.
• Animal models to validate YTHDF3's role and the effect of TRIM2 knockdown.

Main Results:

• High YTHDF3 expression correlates with poor prognosis in UVM.
• YTHDF3 promotes UVM cell proliferation, invasion, and migration.
• TRIM2 is an m6A substrate of YTHDF3, mediating P53 protein degradation via ubiquitination.
• TRIM2 knockdown inhibits YTHDF3-driven tumorigenesis in UVM models.

Conclusions:

• TRIM2, as an m6A-modified substrate of YTHDF3, promotes P53 degradation through the ubiquitin-proteasome system in UVM.
• Targeting the YTHDF3-TRIM2-P53 axis, particularly by silencing TRIM2, can reduce UVM tumorigenic effects.