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首页> 外文期刊>Gut: Journal of the British Society of Gastroenterology >MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor.
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MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor.

机译：MicroRNA-375通过抑制胰岛素样生长因子1受体抑制食管鳞状细胞癌的肿瘤生长和转移。

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BACKGROUND: To understand the involvement of micro-RNA (miRNA) in the development and progression of oesophageal squamous cell carcinoma (ESCC), miRNA profiles were compared between tumour and corresponding non-tumour tissues. METHODS: miRCURY LNA array was used to generate miRNA expressing profile. Real-time quantitative PCR was applied to detectthe expression of miR-375 in ESCC samples and its correlation with insulin-like growth factor 1 receptor (IGF1R). Methylation-specific PCR was used to study the methylation status in the promoter region of miR-375. The tumour-suppressive effect of miR-375 was determined by both in-vitro and in-vivo assays. RESULTS: The downregulation of miR-375 was frequently detected in primary ESCC, which was significantly correlated with advanced stage (p=0.003), distant metastasis (p<0.0001), poor overall survival (p=0.048) and disease-free survival (p=0.0006). Promoter methylation of miR-375 was detected in 26 of 45 (57.8%) ESCC specimens. Functional assays demonstrated that miR-375 could inhibit clonogenicity, cell motility, cell proliferation, tumour formation and metastasis in mice. Further study showed that miR-375 could interact with the 3'-untranslated region of IGF1R and downregulate its expression. In clinical specimens, the expression of IGF1R was also negatively correlated with miR-375 expression (p=0.008). CONCLUSIONS: This study demonstrates that miR-375 has a strong tumour-suppressive effect through inhibiting the expression of IGF1R. The downregulation of miR-375, which is mainly caused by promoter methylation, is one of the molecular mechanisms involved in the development and progression of ESCC.
机译：背景：为了了解微小RNA（miRNA）在食道鳞状细胞癌（ESCC）的发生和发展中的作用，比较了肿瘤和相应的非肿瘤组织的miRNA概况。方法：使用miRCURY LNA阵列产生miRNA表达谱。应用实时定量PCR检测miR-375在ESCC样品中的表达及其与胰岛素样生长因子1受体（IGF1R）的相关性。甲基化特异性PCR用于研究miR-375启动子区域的甲基化状态。通过体外和体内试验确定miR-375的肿瘤抑制作用。结果：在原发性食管鳞癌中经常检测到miR-375的下调，这与晚期阶段（p = 0.003），远处转移（p <0.0001），较差的总生存率（p = 0.048）和无病生存率（p = 0.048）显着相关。 p = 0.0006）。在45个（57.8％）ESCC标本中的26个中检测到miR-375的启动子甲基化。功能测定表明，miR-375可以抑制小鼠的克隆形成性，细胞运动性，细胞增殖，肿瘤形成和转移。进一步的研究表明，miR-375可以与IGF1R的3'-非翻译区相互作用，并下调其表达。在临床标本中，IGF1R的表达也与miR-375的表达负相关（p = 0.008）。结论：本研究证明miR-375通过抑制IGF1R的表达具有很强的肿瘤抑制作用。 miR-375的下调主要由启动子甲基化引起，是ESCC发生和发展的分子机制之一。

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