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首页> 外文期刊>Protoplasma: An International Journal of Cell Biology >TCF4 promotes colorectal cancer drug resistance and stemness via regulating ZEB1/ZEB2 expression
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TCF4 promotes colorectal cancer drug resistance and stemness via regulating ZEB1/ZEB2 expression

机译:TCF4通过调节ZeB1 / Zeb2表达促进结肠直肠癌耐药性和茎秆

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摘要

The present study aims to investigate the roles of TCF4 and its underlying mechanism in colorectal cancer (CRC). Doxorubicin-resistant DLD-1 (DLD1 DR), TCF4 overexpression, and TCF4 knockdown cell lines were constructed. A flow cytometer was used to analyze frequencies of CD133(+) cell in the DLD1 and DLD1 DR cells. Quantitative real-time PCR (qPCR) was used to determine the expressions of cancer stem cell (CSC) makers. Stemness of CRC cells were determined using tumorsphere formation assay. The correlation between TCF4 and ZEB1/ZEB2 were determined using public data from The Cancer Genome Atlas (TCGA) datasets. ZEB1/ZEB2 overexpression cell lines were constructed and cell viabilities were then determined using MTT and colony formation assays. TCF4 overexpression promoted proliferation of CRC cell lines and relative expressions of TCF4 were significantly increased in the DLD1 DR cells. TCF4 overexpression promoted CRC cell doxorubicin resistance, whereas TCF4 knockdown significantly decreased doxorubicin resistance. Additionally, TCF4 overexpression also significantly increased frequencies of CSC cells, expressions of CSC markers, and CRC ability to form tumorsphere. Furthermore, TCF4 promoted ZEB1 and ZEB2 expression, leading to CRC proliferation and doxorubicin resistance. TCF4 promoted CRC doxorubicin resistance and stemness by regulating expressions of ZEB1 and ZEB2.
机译:本研究旨在探讨TCF4及其潜在机制在结肠直肠癌(CRC)中的作用。构建了多柔比蛋白抗性DLD-1(DLD1 DR),TCF4过表达和TCF4敲低细胞系。流式细胞仪用于分析DLD1和DLD1 DR细胞中CD133(+)细胞的频率。定量实时PCR(QPCR)用于确定癌症干细胞(CSC)制造商的表达。使用肿瘤孢子体测定法测定CRC细胞的茎。使用来自癌症基因组Atlas(TCGA)数据集的公共数据确定TCF4和ZEB1 / ZEB2之间的相关性。构建ZeB1 / Zeb2过表达细胞系,然后使用MTT和菌落形成测定测定细胞活力。 TCF4过表达促进CRC细胞系的增殖,DLD1 DR细胞中TCF4的相对表达显着增加。 TCF4过表达促进了CRC细胞的抗性,而TCF4敲低显着降低了多柔比蛋白抗性。另外,TCF4过表达也显着增加了CSC细胞的频率,CSC标记的表达和形成肿瘤的CRC能力。此外,TCF4促进了ZeB1和Zeb2表达,导致CRC增殖和多柔比蛋白抗性。通过调节Zeb1和Zeb2的表达,TCF4促进了CRC多柔比蛋白抗性和茎。

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