GOLPH3通过调控TGF-β信号通路促进甲状腺乳头状癌的机制研究

Abstract

Thyroid cancer incidence is rising globally, with papillary thyroid carcinoma (PTC) being the most common subtype. While most patients have favorable outcomes, a subset develops aggressive, therapy-resistant disease, highlighting an urgent need to understand the molecular drivers of PTC progression. Golgi phosphoprotein 3 (GOLPH3) has emerged as a potential oncogene in multiple solid tumors, yet its functional role and mechanistic basis in PTC remain poorly defined. This study aims to elucidate the biological function of GOLPH3 in PTC progression and investigate whether it exerts oncogenic effects through the TGF-β signaling pathway. qPCR and WB were utilized to determine the expression of GOLPH3 in PTC cells. The KEGG analysis was used to identify the signaling pathways enriched by GOLPH3. CCK-8, flow cytometry, and Transwell assays were respectively utilized to examine the viability, apoptosis level, as well as PTC cells’ migration and invasion abilities. The proportion of senescent cells was analyzed through β-galactosidase staining. WB was applied to detect the expression of TGF-β signaling pathway markers (TGF-β1, SMAD2, p-SMAD2, p-SMAD3, SMAD3) as well as EMT markers (E-cadherin, N-cadherin, Snail). GOLPH3 expression was upregulated in PTC cells. GOLPH3 knockdown mitigated the viability, invasiveness, and motility of cancer cells and elevated the apoptosis rate and the proportion of senescent cells. KEGG analysis demonstrated that GOLPH3 was significantly enriched in the TGF-β signaling pathway, and that GOLPH3 knockdown could inhibit the TGF-β pathway and block the EMT process. Additionally, via activating this pathway, GOLPH3 overexpression promoted PTC progression. However, as an inhibitor of this pathway, LY2109761 could reverse the effects induced by GOLPH3 overexpression. Collectively, these findings establish GOLPH3 as a critical driver of PTC malignancy through TGF-β pathway activation, providing a mechanistic link between Golgi function and cancer si