بیان کاهش یافته Keap1 و اهمیت بالینی-پاتولوژیکی آن در سرطان معده: همبستگی با متیلاسیون DNA در پروموتر

سوزن گر, نرگس and صادقی, محمدرضا and جدی, فرهاد and صمدی, ناصر and حجازی, محمدسعید and آزاد, مهدی and شیرمحمدی, مسعود and صومی, محمدحسین (1398) بیان کاهش یافته Keap1 و اهمیت بالینی-پاتولوژیکی آن در سرطان معده: همبستگی با متیلاسیون DNA در پروموتر. Gazzetta Medica italiana - archivio per le Scienze Mediche ــ 178 (5). pp. 292-300. شاپا 0393-3660

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Decreased expression of the Keap1gene and its clinicopathological significance in gastric cancer: correlation with promoter DNA methylation

English Abstract

BACKGROUND: Kelch–like ECH–associated protein1 (Keap1) is a cytoplasmic anchor of nuclear factor erythroid 2–related factor2 (Nrf2), which mediates the regulation of genes involved in apoptosis and cell survival. Epigenetic events such as aberrant DNA methylation is emerging as a possible mechanism for dysregulation of the Keap1 in cancer. However, the impacts of Keap1 methylation and expression on gastric cancer(GC) development and progression have not yet been investigated. METHODS: We analyzed the Keap1 promoter methylation and its mRNA or protein expression in endoscopic biopsies from 60 GC patients compared with those in non–GC individuals by methylated DNA immunoprecipitation(MeDIP) assay, quantitative real–time PCR and immunohistochemistry, respectively. RESULTS: The methylation level of Keap1 in GC was remarkably higher than that in non–GC biopsies (p<0.001). In contrast, the mRNA and protein expression of Keap1 were clearly down–regulated in GC in comparison with the non–GC tissues (p<0.001). In addition, there were significant differences in both Keap1 methylation or expression levels between the low and high histological grade. Statistical analysis revealed that Keap1 expression inversely correlates to its promoter methylation in GC (r =–0.55, p<0.001). CONCLUSIONS: Our results reflect an epigenetic regulation of Keap1 expression, and highlight the importance of Keap1 downregulation and its promoter hypermethylation in GC pathogenesis.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :نرگس سوزن گر
نویسنده :محمدرضا صادقی
نویسنده :فرهاد جدی
نویسنده :ناصر صمدی
نویسنده :محمدسعید حجازی
نویسنده :مهدی آزاد
نویسنده :مسعود شیرمحمدی
نویسنده :محمدحسین صومی
Additional Information:Indexed in: Scopus, Embase , ESCI
کلیدواژه ها (انگلیسی):Clinical pathology , DNA methylation , Stomach neoplasms , Kelch-like ECH-associated protein 1 , GA-binding protein transcription factor
Subjects:QZ Pathology
WI Digestive System
Divisions:Faculty of Medicine > Department of Basic Sciences > Department of Genetics
ID Code:12403
Deposited By: Dr. Farhad Jeddi
Deposited On:20 Aug 1398 13:24
Last Modified:20 Aug 1398 13:24

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