Association Of RS2620381、RS10061133、RS6513497 With ESCC Risk And Study Of ZBTB8A Function On Human Gastric Cancer Cell AGS

Esophageal cancer is one of the most aggressive cancers in the world, Its morbidity has obvious differences between ethnic groups, especially more common in Asia. Esophageal cancer has two main types: esophageal squamous cell carcinoma(ESCC) and esophageal adenocarcinoma(EADC). The Chinese population mainly in ESCC. Esophageal squamous cell carcinoma(ESCC) is mainly affected by the interaction between genotype and environment. This study was conducted to evaluate the association between miR-627 rs2620381 、 miR-449 b rs10061133 、 miR-646 rs6513497 and ESCC susceptibility in Chinese population.This study included 773 ESCC cancers and 882 healthy controls recruited from east China. By reading the literature and database search, we selected miR-627 rs2620381, miR-449 b rs10061133, and miR-646 rs6513497 these three SNP sites. The rs2620381 site is located in the seed region of miR-627, which is A/C mutation. The rs10061133 site and rs6513497 site are located in miR-449 b and miR-646 maturation sequence, which are A/G and T/G mutations respectively. Genotyping was conducted by using a SNaPshot Multiplex System, and the OR and 95% CI were determined by analysis of regression, which were adjusted by age, sex, smoking and drinking.We found that: 1. mi R-449 b rs10061133(A>G)was associated with ESCC susceptibility. The GG genotype was associated with a significant decreased risk of ESCC compared with the AA/AC genotypes(Correction,OR=0.77, 95% CI: 0.62-0.97). After stratifying by age, sex, drinking and smoking, we found age, sex, drinking and smoking status could affect the association between this locus and ESCC risk. 2. miR-627 rs2620381(A>C)and miR-646 rs6513497(T>G)didn’t show association with ESCC in this population. In addition, through the miR-646 rs6513497 stratified analysis, we found age and drinking status could affect the association between this locus and ESCC.Conclusion: This study provides the first evidence that miR-449 b rs10061133 are associated with ESCC risk in Chinese population. and the association among miR-646 rs6513497、miR-627 rs2620381 and ESCC susceptibility need further study.Meanwhile, in this study, we used the overexpression and depletion of ZBTB8 A to study the effects of ZBTB8 A on the biological function of human gastric cancer cells AGS and its mechanisms. The results showed that: 1.Expression of ZBTB8 A could result in cell cycle arrest in S phase. 2. ZBTB8 A not rely on Cspase-3 pathway but regulate the expression of bcl-2 / bax to promote apoptosis. All of the related work shows that ZBTB8 A is likely to be a transcription inhibitor. It would be helpful for further study the function of ZBTB8 A on AGS cell lines.