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The Sp1-mediaded allelic regulation of MMP13 expression by an ESCC susceptibility SNP rs2252070.


ABSTRACT: Metallopeptidase 13 (MMP13), a well-known and highly regulated zinc-dependent MMP collagenase, plays a crucial part in development and progression of esophageal squamous cell carcinoma (ESCC). Therefore, we examined associations between ESCC susceptibility and four haplotype-tagging single nucleotide polymorphisms (htSNPs) using a two stage case-control strategy. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed by logistic regression model. After analyzing 1588 ESCC patients and frequency-matched 1600 unaffected controls, we found that MMP13 rs2252070 G?>?A genetic polymorphism is significantly associated with ESCC risk in Chinese Han populations (GA: OR?=?0.63, 95% CI?=?0.54-0.74, P?=?1.7?×?10(-6), AA: OR?=?0.73, 95% CI?=?0.66-0.81, P?=?1.8?×?10(-6)). Interestingly, the rs2252070 G-to-A change was shown to diminish a Sp1-binding site in ESCC cells. Reporter gene assays indicated that the rs2252070 A allele locating in a potential MMP13 promoter has low promoter activities. After measuring MMP13 gene expression in sixty-six pairs of esophageal cancer and normal tissues, we observed that the rs2252070 A protective allele carriers showed decreased oncogene MMP13 expression. Results of these analyses underline the support of the notion that MMP13 might function as a key oncogene in esophageal carcinogenesis.

SUBMITTER: Shi M 

PROVIDER: S-EPMC4887914 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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The Sp1-mediaded allelic regulation of MMP13 expression by an ESCC susceptibility SNP rs2252070.

Shi Meng M   Xia Jianhong J   Xing Huaixin H   Yang Wenjun W   Xiong Xiangyu X   Pan Wenting W   Han Sichong S   Shang Jinhua J   Zhou Changchun C   Zhou Liqing L   Yang Ming M  

Scientific reports 20160601


Metallopeptidase 13 (MMP13), a well-known and highly regulated zinc-dependent MMP collagenase, plays a crucial part in development and progression of esophageal squamous cell carcinoma (ESCC). Therefore, we examined associations between ESCC susceptibility and four haplotype-tagging single nucleotide polymorphisms (htSNPs) using a two stage case-control strategy. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed by logistic regression model. After analyzing 1588 ESCC patients  ...[more]

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