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使用RNA测序对结肠直肠癌细胞中癌胚抗原信号进行全基因组分析。

The Genome-Wide Analysis of Carcinoembryonic Antigen Signaling by Colorectal Cancer Cells Using RNA Sequencing.

作者信息

Bajenova Olga, Gorbunova Anna, Evsyukov Igor, Rayko Michael, Gapon Svetlana, Bozhokina Ekaterina, Shishkin Alexander, O'Brien Stephen J

机构信息

Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russia.

Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg, Russia.

出版信息

PLoS One. 2016 Sep 1;11(9):e0161256. doi: 10.1371/journal.pone.0161256. eCollection 2016.

Abstract

Сarcinoembryonic antigen (CEA, CEACAM5, CD66) is a promoter of metastasis in epithelial cancers that is widely used as a prognostic clinical marker of metastasis. The aim of this study is to identify the network of genes that are associated with CEA-induced colorectal cancer liver metastasis. We compared the genome-wide transcriptomic profiles of CEA positive (MIP101 clone 8) and CEA negative (MIP 101) colorectal cancer cell lines with different metastatic potential in vivo. The CEA-producing cells displayed quantitative changes in the level of expression for 100 genes (over-expressed or down-regulated). They were confirmed by quantitative RT-PCR. The KEGG pathway analysis identified 4 significantly enriched pathways: cytokine-cytokine receptor interaction, MAPK signaling pathway, TGF-beta signaling pathway and pyrimidine metabolism. Our results suggest that CEA production by colorectal cancer cells triggers colorectal cancer progression by inducing the epithelial- mesenchymal transition, increasing tumor cell invasiveness into the surrounding tissues and suppressing stress and apoptotic signaling. The novel gene expression distinctions establish the relationships between the existing cancer markers and implicate new potential biomarkers for colorectal cancer hepatic metastasis.

摘要

癌胚抗原(CEA,癌胚抗原相关细胞黏附分子5,CD66)是上皮癌转移的促进因子,被广泛用作转移的预后临床标志物。本研究的目的是确定与CEA诱导的结直肠癌肝转移相关的基因网络。我们比较了具有不同体内转移潜能的CEA阳性(MIP101克隆8)和CEA阴性(MIP 101)结直肠癌细胞系的全基因组转录组谱。产生CEA的细胞在100个基因的表达水平上表现出定量变化(上调或下调)。这些变化通过定量RT-PCR得到证实。KEGG通路分析确定了4条显著富集的通路:细胞因子-细胞因子受体相互作用、MAPK信号通路、TGF-β信号通路和嘧啶代谢。我们的结果表明,结直肠癌细胞产生CEA通过诱导上皮-间质转化、增加肿瘤细胞对周围组织的侵袭性以及抑制应激和凋亡信号来触发结直肠癌进展。新的基因表达差异建立了现有癌症标志物之间的关系,并暗示了结直肠癌肝转移的新潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f5f/5008809/9a68211f2807/pone.0161256.g001.jpg

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