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喉鳞状细胞癌细胞系对小干扰RNA介导的细胞周期蛋白依赖性激酶1(CDK1)基因敲低表现出高度耐受性。

Laryngeal squamous cell carcinoma cell lines show high tolerance for siRNA-mediated CDK1 knockdown.

作者信息

Bednarek Kinga, Kostrzewska-Poczekaj Magdalena, Ustaszewski Adam, Janiszewska Joanna, Kiwerska Katarzyna, Paczkowska Julia, Grenman Reidar, Giefing Maciej, Jarmuz-Szymczak Malgorzata

机构信息

Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.

Department of Tumor Pathology, Greater Poland Cancer Centre Poznan, Poland.

出版信息

Am J Cancer Res. 2021 May 15;11(5):2081-2094. eCollection 2021.

Abstract

Alterations of the cell cycle checkpoints lead to uncontrolled cell growth and result in tumorigenesis. One of the genes essential for cell proliferation and cell cycle regulation is . This makes it a potential target in cancer therapy. In our previous study we have shown upregulation of this gene in laryngeal squamous cell carcinoma (LSCC). Here we analyze the impact of siRNA-mediated knockdown on cell proliferation and viability, measured with cell growth monitoring and colorimetric test (CCK8 assay), respectively. We proved that a reduction of expression by more than 50% has no effect on these cellular processes in LSCC cell lines (n=2). Moreover, using microarrays, we analyzed global gene expression deregulation in these cell lines after knockdown. We searched for enriched ontologies in the group of identified 137 differentially expressed genes (>2-fold change). Within this group we found 3 enriched pathways: protein binding (GO:0005515), mitotic nuclear division (GO:0007067) and transmembrane receptor protein tyrosine kinase signaling pathway (GO:0007169) and a group of 11 genes encoding proteins for which interaction with CDK1 was indicated with the use of bioinformatic tools. Among these genes we propose three: and as potentially dependent on .

摘要

细胞周期检查点的改变会导致细胞生长失控并引发肿瘤发生。细胞增殖和细胞周期调控所必需的基因之一是 。这使其成为癌症治疗中的一个潜在靶点。在我们之前的研究中,我们已经表明该基因在喉鳞状细胞癌(LSCC)中上调。在这里,我们分别通过细胞生长监测和比色试验(CCK8 测定)分析了 siRNA 介导的敲低对细胞增殖和活力的影响。我们证明,在 LSCC 细胞系(n = 2)中,该基因表达降低超过 50%对这些细胞过程没有影响。此外,我们使用微阵列分析了敲低后这些细胞系中的全局基因表达失调情况。我们在鉴定出的 137 个差异表达基因(>2 倍变化)组中搜索富集的本体。在该组中,我们发现了 3 条富集途径:蛋白质结合(GO:0005515)、有丝分裂核分裂(GO:0007067)和跨膜受体蛋白酪氨酸激酶信号通路(GO:0007169)以及一组 11 个编码蛋白质的基因,使用生物信息学工具表明这些蛋白质与 CDK1 相互作用。在这些基因中,我们提出三个: 和 ,它们可能依赖于 。

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