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.

中文翻译：

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TCF4通过调节ZEB1/ZEB2表达促进结直肠癌耐药性和干性

本研究旨在探讨 TCF4 在结直肠癌 (CRC) 中的作用及其潜在机制。构建了耐多柔比星 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) 标记的表达。使用肿瘤球形成测定法测定CRC细胞的干细胞。TCF4 和 ZEB1/ZEB2 之间的相关性是使用来自癌症基因组图谱 (TCGA) 数据集的公共数据确定的。构建了 ZEB1/ZEB2 过表达细胞系，然后使用 MTT 和集落形成试验确定细胞活力。TCF4 过表达促进了 CRC 细胞系的增殖，并且 DLD1 DR 细胞中 TCF4 的相对表达显着增加。TCF4 过表达促进了 CRC 细胞多柔比星耐药，而 TCF4 敲低显着降低了多柔比星耐药。此外，TCF4 过表达还显着增加了 CSC 细胞的频率、CSC 标志物的表达和 CRC 形成肿瘤球的能力。此外，TCF4 促进 ZEB1 和 ZEB2 表达，导致 CRC 增殖和阿霉素耐药。TCF4 通过调节 ZEB1 和 ZEB2 的表达来促进结直肠癌多柔比星抗性和干性。TCF4 过表达还显着增加了 CSC 细胞的频率、CSC 标志物的表达和 CRC 形成肿瘤球的能力。此外，TCF4 促进 ZEB1 和 ZEB2 表达，导致 CRC 增殖和阿霉素耐药。TCF4 通过调节 ZEB1 和 ZEB2 的表达来促进结直肠癌多柔比星抗性和干性。TCF4 过表达还显着增加了 CSC 细胞的频率、CSC 标志物的表达和 CRC 形成肿瘤球的能力。此外，TCF4 促进 ZEB1 和 ZEB2 表达，导致 CRC 增殖和阿霉素耐药。TCF4 通过调节 ZEB1 和 ZEB2 的表达来促进结直肠癌多柔比星抗性和干性。