LncRNA HOTAIR regulates the expression of E-cadherin to affect nasopharyngeal carcinoma progression by recruiting histone methylase EZH2 to mediate H3K27 trimethylation.

BACKGROUND/AIM: There has been increasing evidence for the function of long non-coding RNA (lncRNA) in nasopharyngeal carcinoma (NPC). We aim to delve into the position of lncRNA HOX antisense intergenic RNA (HOTAIR), together with enhancer of zeste homolog 2 (EZH2), E-cadherin and trimethylation of lysine 27 on histone H3 (H3K27me3) in NPC. METHODS: HOTAIR, EZH2, and E-cadherin expression in NPC tissues and cells were tested. NPC cell biological functions were examined through gain-of and loss-of function assays. The mechanism of lncRNA HOTAIR/E-cadherin/EZH2/H3K27 axis in NPC was decoded. RESULTS: LncRNA HOTAIR and EZH2 were highly expressed in NPC, and E-cadherin was lowly expressed. Down-regulation of HOTAIR or EZH2 inhibited NPC cell progression and tumor growth. HOTAIR recruited histone methylase EZH2 to mediate trimethylation of H3K27 and regulated E-cadherin expression. CONCLUSION: HOTAIR inhibits E-cadherin by stimulating the trimethylation of H3K27 to promote NPC cell progression through recruiting histone methylase EZH2.

Genetic association of promoter in GRP78 gene with nasopharyngeal carcinoma in a Chinese population.

BACKGROUND: Emerging evidences were accumulated to support the view that GRP78 might be associated with multiple types of cancer. Given these, the aim of this study is to investigate the relationship between single nucleotide polymorphisms (SNPs) of GRP78 gene promoter and nasopharyngeal carcinoma (NPC). METHODS: Three SNPs (rs3216733, rs17840761 and rs17840762) in GRR78 promoter were estimated in 422 NPC patients and 452 controls. Genotyping was performed using SNaPshot SNP. Serum GRP78 level was performed by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by SPSS 17.0 software. RESULTS: Significant association between rs3216733 polymorphism and NPC was observed (Cd vs. dd: OR = 0.57, 95% CI 0.43-0.76, P < 0.001; CC vs. dd: OR = 0.62, 95% CI 0.39-0.98, P = 0.043; Cd/CC vs. dd: OR = 0.58, 95% CI 0.44-0.76, P < 0.001; C vs. d OR = 0.70, 95% CI 0.57-0.86, P = 0.001). Additionally, we further found that expression were down-regulated in serum of patients with NPC carrying rs3216733 CC genotype when compared to that of dd genotype (P < 0.001). CONCLUSION: The observations suggest that rs3216733 polymorphism in the GRP78 gene promoter may correlate with NPC susceptibility.

Genetic polymorphisms in interleukin 13 gene with the susceptibility to nasopharyngeal carcinoma in a Chinese population.

Although inflammation is emerging as a candidate risk factor in tumorigenesis of nasopharyngeal carcinoma (NPC). In particular, Interleukin (IL) 13 involved inflammatory diseases and cancers. Single nucleotide polymorphisms in IL-13 have been associated with multiple cancers. The study analyzed genetic polymorphisms in IL-13 aiming to investigate its' potential susceptibility with the NPC. The genotyping of polymorphisms (rs20541, rs1295687 and rs2069744) was examined by Snapshot SNP and DNA sequencing. All SNPs were within Hardy-Weinberg equilibrium and each appeared in three genotypes in NPC and controls. Adjusted logistic regression showed that the TT genotype of rs20541 increased the risk of lymph node metastasis (TT vs. CC: OR = 2.87, 95%CI, 1.33-6.18, P = 0.007). CT/CC genotypes were associated with the decreased the risk of lymph node metastasis in NPC (CT/CC vs. TT: OR = 0.32, 95%CI, 0.16-0.65, P = 0.002). The concentration of IL-13 was significantly elevated in NPC patients compared with controls (P = 0.012). Moreover, significant differences were detected in the T-C-T haplotype distribution between NPC patients and controls (OR = 2.47, 95%CI, 1.06-5.78, P = 0.031). Our results, the first report, provide evidence that rs20541 polymorphisms may affect the lymph node metastasis of NPC patients in Chinese population.