• THOC3 is significantly upregulated in NSCLC tissues and cell lines, and its high expression correlates with advanced tumor stages and poor patient prognosis, supporting its potential as a prognostic biomarker. • Functional experiments (loss-of-function and gain-of-function) demonstrate that THOC3 enhances NSCLC cell proliferation, migration, and tumorigenicity while suppressing apoptosis in vitro and in vivo . • Mechanistically, THOC3 promotes epithelial-to-mesenchymal transition (EMT) and NSCLC progression by activating the STAT3 signaling pathway, which is validated by rescue experiments using the STAT3 activator Garcinone D. Located on chromosome 5, the THOC3 gene encodes a protein of 351 amino acids, though its precise biological role in various malignancies, including lung cancer (LC), remains to be fully clarified. Elevated expression of THOC3 was observed in LC (IHC) analyses. Increased THOC3 levels were associated with advanced tumor stages and poorer prognosis in patients. Functional studies using both loss-of-function and gain-of-function approaches suggested that THOC3 may influence cellular proliferation, tumorigenic potential, and apoptosis in vitro . Mechanistically, its effects appear to involve activation of the STAT3 pathway. Additionally, Garcinone d -induced STAT3 activation mitigated certain malignant characteristics of LC cells, though silencing THOC3 reversed this effect. These results indicate that THOC3 may serve as a potential prognostic marker and could warrant further investigation as a therapeutic target in LC.
Ni et al. (Sun,) studied this question.