ABSTRACT
Enhancer of Zeste Homologue 2 (EZH2) as a histone methyltransferase epigenetically regulates laryngeal carcinoma (LGC) progression. The present study sought to explore the role and mechanism of EZH2 in the epithelial-mesenchymal transition (EMT) of LGC cells. Expressions of EZH2, secreted frizzled-related protein 1 (SFRP1), and trimethylation of lysine 27 on histone H3 (H3K27me3) in LGC tissues or cells were detected via reverse transcription quantitative polymerase chain reaction (qRT-PCR) and western blotting. Upon transfection of si-EZH2, si-SFRP1, oe-SFRP1, or H3K27me3 upregulation, cell viability was assessed via cell counting kit-8, protein levels of E-cadherin, N-cadherin, ß-catenin, c-Myc, and Cyclin D1 were determined via western blotting, and Vimentin expression was determined via immunofluorescence. The enrichment level of H3K27me3 in the SFRP1 promoter was measured via chromatin immunoprecipitation-PCR. EZH2 was highly expressed in LGC tissues and cells. Silencing EZH2 repelled the EMT of LGC cells. Mechanically, EZH2 upregulated H3K27me3 in the SFRP1 promotor to inhibit SFRP1 expression, and SFRP1 overexpression inactivated the Wnt pathway. H3K27me3 upregulation or SFRP1 downregulation reversed the inhibition of silencing EZH2 in the EMT of LGC cells. Overall, EZH2 upregulated H3K27me3 in the SFRP1 promoter to inhibit SFRP1 expression and activate the Wnt pathway, thereby facilitating the EMT of LGC cells.
Subject(s)
Carcinoma , Laryngeal Neoplasms , Cell Line, Tumor , Enhancer of Zeste Homolog 2 Protein/genetics , Epigenesis, Genetic , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Histones , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins , Laryngeal Neoplasms/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolismABSTRACT
BACKGROUND: The aim of this study was to investigate the association between polymorphism of the cytochrome P450 1B1 (CYP1B1) gene, a metabolic enzyme gene, and the susceptibility to laryngeal cancer among the Chinese Han population. MATERIAL/METHODS: In a case-control study, we investigated polymorphisms in the CYP1B1 gene (rs10012, rs1056827, and rs1056836) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 300 Chinese Han patients with laryngeal cancer and 300 healthy Chinese Han subjects in a control group. We also studied the interactions between genetic polymorphism and risk factors such as smoking and alcohol consumption in the pathogenesis of laryngeal cancer. RESULTS: There were statistically significant differences in the distributions of the rs1056827 and rs1056836 genotypes between the 2 groups. Regarding rs1056827, carriers of the T allele had a significantly higher risk of laryngeal cancer than the G-allele carriers (OR=1.4339, 95% CI: 1.1268-1.8247; P=0.0034). The difference was still statistically significant after adjusting for factors such as age, sex, smoking, and drinking (adjusted OR=1.743, 95% CI: 1.124-3.743, P<0.001). However, regarding rs1056836, the G allele carriers had a significantly lower risk of laryngeal cancer than the C allele carriers (OR=0.5557, 95% CI: 0.3787-0.8154; P=0.0027). The difference was statistically significant even after adjusting for factors such as age, sex, smoking, and drinking (adjusted OR=0.5641, 95% CI: 0.3212-0.8121, P=0.001). Subjects who carry the C-T-C haplotype have a significantly increased incidence of laryngeal cancer. We also found that CYP1B1 rs1056827 polymorphism had synergistic effects with smoking or alcohol consumption regarding the risk of laryngeal cancer. CONCLUSIONS: CYP1B1 gene polymorphism is closely related to the onset of laryngeal cancer. There is a mutually synergistic effect between smoking, alcohol consumption, and CYP1B1 gene polymorphisms regarding laryngeal cancer.
