| Background & Aims Chromosome 1 open reading frame 10 (Clorf10) is either downregulated or absent in esophageal squamous cell carcinoma (ESCC) tissues compared to its corresponding normal counterparts, and it is involved in heat shock and ethanol response and is expected to protect esophageal epithelium from damage. We tested whether genetic variants in the Clorf10 are associated with susceptibility to ESCC.Methods In the present study, we sequenced DNA samples from 32 healthy individuals to search for genetic variants in the promoter region, coding region, and the untranslated region of Clorf10. Genotypes were analyzed in 991 patients and 984 controls. Odds ratios (ORs) and 95%confidence intervals (CIs) were estimated by logistic regression. Luciferase assays were carried out to find the functional SNPs.Results Six strongly linked single nucleotide polymorphisms (SNPs) spanning a region of 7 kb,-1747G/T,-1139G/C,-1079G/A,-900G/T, Gly480Ser, and 4666G/A were identified (D'= 1, r2= 1). Only one SNP-1139G/C was selected to analyze the association between Clorf10 genotypes and risk of ESCC. Subjects with the-1139CC genotype had a greater risk of developing ESCC compared with those with the-1139GG genotype (adjusted OR= 1.34; 95% CI,1.02-1.76). There appears to be an interaction between the-1139G/C polymorphism and tobacco smoking that contributes to the risk for ESCC. However, we did not detect any obvious difference in reporter gene assay driven by each allele of ClorflO promoter or 3'UTR.Conclusion These data showed that Clorf10 haplotypes containing-1747G/T,-1139G/C,-1079G/A,-900G/T, Gly480Ser, and 4666G/A are significantly associated with susceptibility to ESCC. Background & Aims Inhibitor of differentiation or DNA binding 1 (ID1) is one of the HLH (helix-loop-helix) proteins. Elevated ID1 expression either at transcriptional or translational levels has been reported in over 20 types of human cancers and its expression levels are associated with advanced tumour stage. Recent study revealed its roles in multiple processes that are deregulated in cancer cells, including growth factor independence, blockade of differentiation, and attenuation of apoptosis. Therefor, development of drugs that target IDl and its downstream signaling pathways in cancer is a promising therapeutic strategy. Here we investigated the expression change of ID1 in the tumor cells treated with etoposide, cisplatin and UV irradiation, and we also studied the role of ID1 during etoposide induced apoptosis.Methods In the present study, upon onset of apoptosis induced by various kinds of inducers such as etoposide, cisplatin and UV irradiation, the expression level of IDl was detected by Western blot and Real Time PCR. We also analyzed the half-life of IDl protein, the transcriptional level and stability of ID1 mRNA respectively by cycloheximide inhibition test, luciferase reporter assay and RT-PCR. Annexin-V assay was carried out to evaluate the contribution of IDl protein to etoposide induced apoptosis.Results ID1 expression presented a profound down-regulation in HCT116 and EC9706 cell lines treated with etoposide, cisplatin and UV irradiation. Upon etoposide treatment, ID1 expression level decreased via induction of mRNA instability, but not the transcriptional regulation or protein degradation changes. Additionally, ectopic expression of ID1 in HCT116 cells alleviated etoposide-induced apoptosis.Conclusions These observations indicate that the treatment of etoposide reduces the amount of ID1 by induction of mRNA instability, and exogenously expressed ID1 protects cells against etoposide-induced apoptosis.
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