Gene expression profiling and construction of a putative gene regulatory network of bladder cancer tumor-initiating cells.

Gene expression profiling and construction of a putative gene regulatory network of bladder cancer tumor-initiating cells.
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膀胱癌肿瘤起始细胞的基因表达谱和假定基因调控网络的构建

DOI:
10.18632/oncotarget.22771
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发表时间:
2017-12-19
期刊:
影响因子:
--
通讯作者:
Li C
Li C
中科院分区:
其他
文献类型:
--
作者:
Xin Z;Yang Z;Xu J;Li C;Shao T;Wang G;Li C

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人类膀胱癌肿瘤已被证明包含一个具有干细胞样特征的细胞亚群,这些细胞可能引发肿瘤生长、复发和转移。这些细胞被称为肿瘤启动细胞(tic),将是有效的诊断工具和有价值的治疗靶点。在这里,我们报道了从7种膀胱癌细胞系中分离出的tic,并表明不同来源的tic在体外形成肿瘤球的能力和体内产生异种移植物的能力不同,这表明它们具有显著的异质性。我们使用Affymetrix PrimeView™人类基因表达阵列分析膀胱tic的基因表达谱,这可能有助于了解它们的致瘤能力,并开发专门针对这些细胞的新疗法。然后,我们构建了一个转录因子-基因调控网络,其中包括参与细胞存活、分化、增殖和凋亡的三个关键转录因子。我们通过分析24个临床组织中该网络中关键基因的mRNA表达来验证我们的发现。我们的研究结果表明,这种转录因子-基因调控网络可能有助于开发膀胱癌的临床诊断工具和治疗方法。
Human bladder cancer tumors have been shown to contain a subpopulation of cells with stem-like characteristics that may trigger tumor growth, recurrence, and metastasis. These cells, known as tumor-initiating cells (TICs), would be effective diagnostic tools and valuable therapeutic targets. Here, we report the isolation of TICs from seven bladder cancer cell lines and show that TICs from different sources vary on their ability to form tumorspheres in vitro and generate xenografts in vivo, which suggest they are remarkably heterogeneous. We used the Affymetrix PrimeView™ Human Gene Expression Array to analyze gene expression profiles of bladder TICs, which may help understand their tumorigenic capacities and develop novel treatments specifically targeted toward these cells. We then constructed a transcription factor-gene regulatory network that includes three key transcription factors that are involved in cell survival, differentiation, proliferation, and apoptosis. We validated our findings by analyzing mRNA expression of the key genes in this network in 24 clinical tissues. Our results suggest that this transcription factor-gene regulatory network could be useful in the development of clinical diagnostic tools and therapy approaches for bladder cancer.
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