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微小 RNA 与食管鳞状细胞癌。

MicroRNAs and esophageal squamous cell carcinoma.

机构信息

Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki 852-8501, Japan.

出版信息

Digestion. 2010;82(3):138-44. doi: 10.1159/000310918. Epub 2010 Jun 25.

Abstract

Esophageal cancer is a common cause of cancer death worldwide. Esophageal squamous cell carcinoma (ESCC) is the most predominant type. Certain microRNAs (miRNAs) function in tumorgenesis involved in important biological and pathologic processes. To reveal miRNAs' signatures of ESCC, we analyzed miRNAs extracted from ESCC cell lines with the microRNA microarray. The significant alterations were confirmed by quantitative real-time PCR using miRNAs extracted from cell lines or patients' esophageal biopsy tissues. We found that miR-205 and miR-10a were significantly altered in cellular expression, and might be specific for ESCC with potential roles in the pathogenesis. As a result of function studies in miR-205, alterations in miR-205 expression could modulate the phenotype of epithelial cells towards epithelial-mesenchymal transition characterized by reduced abundance of E-cadherin, that is the ESCC-specific miRNA target and inhibit translationally a representative E-cadherin repressor, ZEB1 and ZEB2. Similarly, miR-10a is reported as a tumor suppressor by controlling cell migration/invasion, as it can target homeobox genes. These results provide insight into the potential mechanisms of ESCC in the pathogenesis. This review also includes a comprehensive overview of the relationship between miRNAs and ESCC.

摘要

食管癌是全球癌症死亡的常见原因。食管鳞状细胞癌(ESCC)是最主要的类型。某些 microRNAs(miRNAs)在涉及重要生物学和病理学过程的肿瘤发生中发挥作用。为了揭示 ESCC 的 miRNA 特征,我们使用 microRNA 微阵列分析了从 ESCC 细胞系中提取的 miRNAs。通过使用从细胞系或患者食管活检组织中提取的 miRNAs 进行定量实时 PCR 验证了显著变化。我们发现 miR-205 和 miR-10a 在细胞表达中发生显著改变,可能是 ESCC 的特异性标志物,在发病机制中具有潜在作用。作为 miR-205 功能研究的结果,miR-205 表达的改变可以调节上皮细胞的表型向具有上皮-间充质转化特征的表型,其特征是 E-钙黏蛋白丰度降低,这是 ESCC 特异性 miRNA 靶标,并抑制 E-钙黏蛋白的代表性抑制剂 ZEB1 和 ZEB2 的翻译。同样,miR-10a 通过控制细胞迁移/侵袭被报道为一种肿瘤抑制因子,因为它可以靶向同源盒基因。这些结果为 ESCC 在发病机制中的潜在机制提供了深入了解。这篇综述还包括对 miRNAs 与 ESCC 之间关系的全面概述。

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