TRIM35 inhibits endometrial cancer progression via ubiquitination and degradation of EIF3E

Endometrial carcinoma (EC), recognized as the predominant gynecologic malignancy, is associated with substantial mortality rates. While chemotherapy serves as a critical component in adjuvant and primary treatments, existing pharmacological interventions demonstrate limited efficacy in significantly extending overall survival. Consequently, deciphering the molecular mechanisms driving EC pathogenesis is essential for developing innovative therapies. Existing evidence implicates TRIM35 in tumor proliferation, invasion, and metastatic processes across multiple cancers. To investigate TRIM35's role in EC, we performed integrated bioinformatics analysis followed by experimental validation via RT-qPCR and western blotting, which confirmed its significant downregulation in EC tissues. Subsequently, we transfected endometrial cancer cells with lentiviral plasmids overexpressing TRIM35 to investigate its Impact on cellular proliferation, cell cycle, invasion, and migration. We found that overexpressing TRIM35 significantly inhibited proliferation, invasion, and migration. Further research revealed that TRIM35 regulates the ubiquitination of EIF3E. Additionally, TRIM35 modulates the CDK4/Cyclin D1 signaling pathway, suppressing EC cell proliferation. Intriguingly, overexpressing EIF3E reversed the inhibitory effects of TRIM35 in EC cells. In conclusion, our study demonstrates that TRIM35 regulates the ubiquitination of EIF3E and inhibits the CDK4/Cyclin D1 signaling pathway, thereby suppressing the malignant proliferation of EC. These findings suggested that TRIM35 has potential as a therapeutic target for EC.