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胃癌中 microRNAs 的异常表达及其生物学意义 miR-574-3p

Aberrant expression of microRNAs in gastric cancer and biological significance of miR-574-3p.

机构信息

Department of Pathogenobiology, Jilin University, Changchun, Jilin, China.

出版信息

Int Immunopharmacol. 2012 Aug;13(4):468-75. doi: 10.1016/j.intimp.2012.05.016. Epub 2012 Jun 7.

Abstract

The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying the mechanisms, diagnosis and treatments of cancer. In this study, we employed AFFX miRNA expression chips to search for miRNAs that may be aberrantly expressed in gastric cancer tissues and to investigate the potential roles that miRNAs may play in the development and progression of gastric cancer. 14 miRNAs were found to be down-regulated and 2 miRNAs up-regulated in gastric cancer tissues compared to the normal gastric tissues. Among the aberrantly expressed miRNAs, miR-574-3p was selected to further study its expression features and functional roles. Interestingly, the reduced expression of miR-574-3p occurred mainly in the early stages of gastric cancer or in cancers with high level of differentiation, suggesting that it can be used as a marker for a mild case of gastric cancer. Functional study revealed that cell proliferation, migration and invasion were significantly inhibited in miR-574-3p-transfected gastric cancer SGC7901 cells. Computational prediction and experimental validation suggest that Cullin2 may be one of the targets of miR-574-3p. Overall our study suggests that the aberrantly expressed miRNAs may play regulatory and functional roles in the development and progression of gastric cancer.

摘要

微小 RNA(miRNA)的发现为研究癌症的发生机制、诊断和治疗提供了新的有力工具。本研究采用 AFFX miRNA 表达芯片,筛选胃癌组织中可能异常表达的 miRNA,并探讨其在胃癌发生发展过程中可能发挥的作用。与正常胃组织相比,胃癌组织中发现 14 个 miRNA 下调,2 个 miRNA 上调。在这些异常表达的 miRNA 中,选择 miR-574-3p 进一步研究其表达特征和功能作用。有趣的是,miR-574-3p 的表达下调主要发生在胃癌的早期或高分化癌症中,提示其可作为胃癌轻度病例的标志物。功能研究显示,miR-574-3p 转染的胃癌 SGC7901 细胞的增殖、迁移和侵袭能力显著受到抑制。计算预测和实验验证提示 Cullin2 可能是 miR-574-3p 的一个靶基因。综上所述,本研究表明异常表达的 miRNA 可能在胃癌的发生发展中发挥调节和功能作用。

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