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Archive > Volume 24 Issue 7 > 2017,24(7):708-715. DOI:10.3872/j.issn.1007-385X.2017.07.003 Prev Next
Monographic Report
Effect of aberrant methylation of DACT1 gene different regions on prognosis of the patients with esophageal squamous cell cancer
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Abstract:
Objective: To investigate the methylation status of dishevelled-binding antagonist of beta-catenin 1 (DACT1) gene in CpG islands shore and transcription start site(TSS) regions in esophageal squamous cell cancer (ESCC) cell lines and ESCC samples, and to explore the possible effect on gene transcription and the prognosis of ESCC patients. Methods: MSP and RT-PCR methods were applied respectively to examine the methylation of DACT1 gene in two regions and its mRNAexpression in ESCC cell lines (TE1，TE13，T.Tn，Eca109) andESCC sam- ples which from the high risk area of upper digestive tract cancer in Hebei Province. Results: The negative or weak expression of DACT1 mRNA was detected in four ESCC cell lines. After treated with 5-aza-2'-deoxycytidine (5-aza-dC, a demethylation agent), the expression level of DACT1 mRNA was obviously increased. Meanwhile, The result of MSP showed that the methylation bands were obviously weakened or disappeared. The level of DACT1 mRNA expression had no obviously change after treated with trichostatin A（TSA）. Decreased mRNA expression of DACT1 was observed in ESCC tumor tissues comparing with non-cancerous tissues(P<0.01), and associated with the methylation status of TSS region(P<0.01). The hypermethylation of DACT1 in CpG islands shore region was ob- served both in tumor and corresponding adjacent tissues but wasn’t related to the transcriptional inhibition of DACT1. The result of survival analysis showed that the methylation status of DACT1 in TSS region was associated with ESCC patients’prognosis(P<0.01). Conclusion: The highpermethylation of DACT1 in TSS region was one of the mechanisms causing genes silencing in ESCC and may serve as prognostic methylation biomarkers for ESCC pa- tients.
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Project Supported:
Project supportedby theNa-tional NatureScienceFoundationofChina(No.81472335,No. 81572441), and the Natures Science Foundation of Hebei Province (No. H2013206315)
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