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[人食管癌细胞与人脐间充质干细胞融合后转录组变化的比较分析]

[A comparative analysis of the changes of transcriptome after fusion of esophageal cancer cells with human umbilical mesenchymal stem cells].

作者信息

Wang Yong, Zhou Bing, Fan Hongbin, Yu Long, Guo Liping, Lu Shixin

机构信息

Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.

Email:

出版信息

Zhonghua Zhong Liu Za Zhi. 2014 Oct;36(10):726-32.

Abstract

OBJECTIVE

To compare the transcriptome of esophageal cancer cells (EC9706), human mesenchymal stem cells (MSCs), and after fusion of esophageal cancer cells with MSCs, and to further study their different expression profiles and the changes of their signaling pathways.

METHODS

We examined the gene expression profiles of these cells with transcriptome microarray using LIMMA package and several web-based applications, such as DAVID, ToppGene and MSigDB. The resulting sets of differentially expressed genes (DEGs) were comprehensively analyzed to identify the pathways and their changes after the cell fusion.

RESULTS

A total of 4 548 significantly DEGs among the three cell lines were found by LIMMA. Three functional annotation web tools predicted that DNA damage repair, cell cycle arrest and apoptosis pathways were enriched. Total DEGs were mapped to the canonic pathways with KEGGanim which depicted that the core genes of DNA damage repair, cell cycle arrest and pro-apoptosis were up-regulated in fusion cells, and they mightbe combined to respond the fusion-induced damage stress. The up-regulation of suppressive factor DUSP6 might feedback inhibit the MAPK signaling pathway in the fusion cells, too.

CONCLUSIONS

Transcriptome analysis suggests that hMSCs and EC9706 cell fusion may inhibit growth of EC cells by induction of pro-apoptotic signaling and DUSP6 negative feedback inhibition mechanism. In addition, the changes of immune regulation-related and differentiation-related genes indicate that the fusion cells inherited certain immune-suppressive function from the stem cells.

摘要

目的

比较食管癌细胞(EC9706)、人间充质干细胞(MSCs)以及食管癌细胞与MSCs融合后的转录组,进一步研究它们不同的表达谱及其信号通路的变化。

方法

我们使用LIMMA软件包以及几个基于网络的应用程序,如DAVID、ToppGene和MSigDB,通过转录组微阵列检测这些细胞的基因表达谱。对所得的差异表达基因(DEGs)集进行综合分析,以确定细胞融合后信号通路及其变化。

结果

通过LIMMA在三种细胞系中总共发现了4548个显著差异表达基因。三个功能注释网络工具预测DNA损伤修复、细胞周期阻滞和凋亡信号通路显著富集。利用KEGGanim将所有差异表达基因映射到经典信号通路,结果显示DNA损伤修复、细胞周期阻滞和促凋亡的核心基因在融合细胞中上调,它们可能共同作用以应对融合诱导的损伤应激。抑制因子DUSP6的上调也可能在融合细胞中反馈抑制MAPK信号通路。

结论

转录组分析表明,hMSCs与EC9706细胞融合可能通过诱导促凋亡信号和DUSP6负反馈抑制机制来抑制食管癌细胞的生长。此外,免疫调节相关基因和分化相关基因的变化表明,融合细胞继承了干细胞的某些免疫抑制功能。

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