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利用 SW1116 细胞系比较结肠癌干细胞与非干细胞的 miRNA 表达谱。

miRNA expression profile of colon cancer stem cells compared to non-stem cells using the SW1116 cell line.

机构信息

Department of General Surgery, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, PR China.

出版信息

Oncol Rep. 2012 Dec;28(6):2115-24. doi: 10.3892/or.2012.2054. Epub 2012 Sep 24.

Abstract

Colorectal cancer (CRC) is one of the major causes of cancer-related mortality worldwide. Recent studies revealed that there is a relationship between CRC occurrence and microRNA (miRNA) function. Stem cells are a type of cells that have the ability to self-renew and to proliferate extensively while maintaining the undifferentiated state. Cancer stem cells (CSCs) are closely linked to tumor recurrence and metastasis. To this end, we evaluated the miRNA expression differences between colon CSCs and non-stem cells using the SW1116 cell line, to determine the relationship between tumor stem cells and tumor biological behavior. We isolated populations of colon CSCs with the CD133+/CD44+ and CD133-/CD44- surface phenotype from a human SW1116 colon adenocarcinoma cell line using flow cytometry. The expression of miRNA and mRNA of both sets of cells was examined with miRNA and mRNA arrays. Bioinformatic methods were used to analyze microarray results. We completed gene ontology analysis, pathway analysis, miRNA target gene prediction with databases. We identified a colon stem cell miRNA expression profile comprising 31 upregulated and 31 downregulated miRNAs, such as miR29a, miR29b, miR449b and miR4524. Some of these differentially expressed miRNAs may be involved in the regulation of stem cell differentiation. Gene ontology and pathway analyses showed that the differences are closely related to the function of the cell cycle, cell differentiation, signaling pathway, cytoskeletal proteins and cell-matrix adhesion in colon cancer stem cells. We found that miRNAs play an important role in regulating the expression of colon CSC characteristics. By regulating the expression of CSC signaling pathways, cytoskeleton and membrane proteins, miRNAs give tumor stem cells the macrobiological behavior of recurrence and metastasis. This study provides a new perspective on CRC metastasis and recurrence.

摘要

结直肠癌(CRC)是全球癌症相关死亡率的主要原因之一。最近的研究表明,CRC 的发生与 microRNA(miRNA)功能之间存在关系。干细胞是一种具有自我更新和广泛增殖能力的细胞,同时保持未分化状态。癌症干细胞(CSC)与肿瘤复发和转移密切相关。为此,我们使用 SW1116 细胞系评估了结肠 CSC 和非干细胞之间的 miRNA 表达差异,以确定肿瘤干细胞与肿瘤生物学行为之间的关系。我们使用流式细胞术从人 SW1116 结肠腺癌细胞系中分离出 CD133+/CD44+和 CD133-/CD44-表面表型的结肠 CSC 群体。使用 miRNA 和 mRNA 芯片检测两组细胞的 miRNA 和 mRNA 表达。使用生物信息学方法分析微阵列结果。我们完成了基因本体分析、通路分析、数据库预测 miRNA 靶基因。我们确定了一个包含 31 个上调和 31 个下调 miRNA 的结肠干细胞 miRNA 表达谱,如 miR29a、miR29b、miR449b 和 miR4524。这些差异表达的 miRNA 中的一些可能参与调节干细胞分化。基因本体和通路分析表明,这些差异与结肠癌干细胞中细胞周期、细胞分化、信号通路、细胞骨架蛋白和细胞-基质黏附的功能密切相关。我们发现 miRNA 在调节结肠 CSC 特征的表达中发挥重要作用。通过调节 CSC 信号通路、细胞骨架和膜蛋白的表达,miRNA 赋予肿瘤干细胞复发和转移的宏观生物学行为。本研究为 CRC 转移和复发提供了新的视角。

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