UBE2T promotes papillary thyroid carcinoma progression by activating the JAK/STAT3 pathway via negative regulation of SOCS2.

Papillary thyroid carcinoma (PTC) exhibits aggressive behaviors such as tumor invasion and lymph node metastasis that critically influence prognosis, yet reliable predictors of invasiveness remain elusive. This study investigated the molecular mechanisms through which ubiquitin-conjugating enzyme E2T (UBE2T) drives PTC progression. Bioinformatics analysis of TCGA/GEO datasets and validation with institutional clinical samples revealed UBE2T overexpression correlated with advanced clinicopathological features. Functional experiments demonstrated that UBE2T overexpression enhanced PTC cell invasiveness, while its knockdown suppressed malignant behaviors. Mechanistically, co-immunoprecipitation identified cytokine signaling suppressor 2 (SOCS2) as a key interactor mediating UBE2T's effects on JAK-STAT3 pathway activation. Rescue experiments and immunofluorescence confirmed UBE2T promotes oncogenesis by destabilizing SOCS2, thereby relieving its inhibition of STAT3 phosphorylation. These findings establish UBE2T as a novel regulator of PTC progression through SOCS2/JAK-STAT3 axis manipulation, providing potential therapeutic targets to mitigate metastasis and recurrence in aggressive thyroid carcinomas.