Abstract
OBJECTIVES: To investigate the expression of Golgi membrane protein 1 (GOLM1) in oral squamous cell carcinoma (OSCC) and its effects on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in OSCC cells and the underlying mechanisms. METHODS: Bioinformatics analysis was performed using the data from The Cancer Genome Atlas and Genotype-Tissue Expression databases to evaluate the expression of GOLM1 in head and neck squamous cell carcinoma (HNSCC) and its prognostic significance. Immunohistochemistry was used to detect GOLM1 expression in OSCC tissues and adjacent tissues. The mRNA and protein levels of GOLM1 in human normal oral keratinocytes (HOK) and OSCC cell lines (HSC-3 and SCC-25, respectively) were measured via real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot. For in vitro experiments, GOLM1 was silenced in HSC-3 and SCC-25 cells via lentiviral transfection, with the transfection efficiency validated through qRT-PCR and Western blot. Cell proliferation was assessed through Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell migration and invasion were evaluated via wound healing and Transwell assays, respectively. Western blot was used to analyze EMT-related proteins (E-cadherin, N-cadherin, and Vimentin). Gene set enrichment analysis (GSEA) was conducted to identify potential signaling pathways associated with GOLM1, followed by validation through Western blot and rescue experiments. RESULTS: GOLM1 exhibited a high expression in HNSCC, correlation with poor prognosis, and significant upregulation in OSCC tissues. In addition, GOLM1 showed markedly elevated expression levels in OSCC cell lines HSC-3 and SCC-25 compared with those in HOK cells. Silencing of GOLM1 markedly suppressed OSCC cell proliferation, migration, and invasion, accompanied with an increased E-cadherin expression and decreased N-cadherin and Vimentin levels. GSEA revealed a strong association between GOLM1 and the transforming growth factor-beta (TGF-β) signaling pathway. Silencing of GOLM1 reduced the expressions of TGF-β1, Smad2, and phosphorylated Smad2. Exogenous recombinant human TGF-β1 protein rescued the inhibitory effects of GOLM1 knockdown on OSCC cell proliferation, migration, and invasion. CONCLUSIONS: GOLM1 is overexpressed in OSCC tissues and cells, and silencing of this protein inhibits OSCC cell proliferation, migration, invasion, and EMT via the TGF-β1/Smad2 signaling pathway.