Epigenetic network of EZH2/SFRP1/Wnt in the epithelial-mesenchymal transition of laryngeal carcinoma cells.

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.

Restoration of secreted frizzled-related protein 1 suppresses growth and increases cisplatin sensitivity in laryngeal carcinoma cells by downregulating NHE1.

It has been documented that secreted frizzled-related protein 1 (SFRP1) is epigenetically silenced in laryngeal carcinoma. However, the function of SFRP1 in laryngeal carcinoma remains elusive. In this study, we performed gain-of-function studies to determine the roles of SFRP1 in laryngeal carcinoma growth, tumorigenesis, and cisplatin resistance. Laryngeal carcinoma cell lines were treated with 5-aza-2'-deoxycytidine (5-aza-dC) and examined for SFRP1 expression. The effects of overexpression of SFRP1 on cell proliferation, colony formation, apoptosis, tumorigenesis, and cisplatin sensitivity were assessed. It was found that 5-aza-dC exposure significantly induced the expression of SFRP1 in both Hep-2 and SNU899 laryngeal carcinoma cells. Ectopic expression of SFRP1 significantly decreased cell proliferation and colony formation in vitro and retarded xenograft tumor growth in vivo. SFRP1-overexpressing Hep-2 cells displayed a higher percentage of apoptosis and enhancement of caspase-3 cleavage, which was coupled with loss of Δψm and increased release of cytochrome c from the mitochondria to the cytosol. Moreover, SFRP1 overexpression sensitized laryngeal carcinoma cells to cisplatin and decreased intracellular pH values. Mechanistically, SFRP1 inhibited the expression of Na+/H+ exchanger 1 (NHE1) and overexpression of NHE1 reversed the suppressive activity of SFRP1 on laryngeal carcinoma cells. In conclusion, we demonstrate that SFRP1 induces mitochondrial apoptosis and increases cisplatin sensitivity in laryngeal carcinoma cells via downregulation of NHE1. Delivery of SFRP1 may offer therapeutic benefits in the treatment of laryngeal carcinoma.

GSTM1 null polymorphisms is associated with laryngeal cancer risk: a meta-analysis.

Many studies have examined the association between the GSTM1 (null or non-null genotype) polymorphism and laryngeal cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. PubMed was searched for case-control studies published up to December 2013. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 23 studies, comprising 2,562 laryngeal cancer cases and 4,091 controls, were included. Overall, for null versus present, the pooled OR was 1.22 (95 % CI = 1.10-1.36), and the heterogeneity was found in all studies. In the stratified analysis by ethnicity, significant risks were found among Asians (OR = 1.71; 95 % CI = 1.34-2.19; P = 0.011 for heterogeneity) and in Caucasians (OR = 1.13, 95 % CI = 1.00-1.27; P = 0.036 for heterogeneity). In conclusion, this meta-analysis demonstrates that the GSTM1 null gene polymorphism is an increased risk of laryngeal cancer in Asians and Caucasians.