The transcription factor forkhead box Q1 (FoxQ1) is overexpressed in different solid tumors including breast cancer, but the mechanism underlying its oncogenic function is still not fully understood. In this study, we compared RNA‐seq data from FoxQ1 overexpressing SUM159 cells with that of empty vector‐transfected control cells to identify novel mechanistic targets of this transcription factor. Analysis of The Cancer Genome Atlas (TCGA) data set revealed significantly higher expression of FoxQ1 in black breast cancer patients compared with white women with this disease. In contrast, expression of FoxQ1 was comparable in ductal and lobular carcinomas in the breast cancer TCGA data set. Complementing our published findings in basal‐like subtype, immunohistochemistry revealed upregulation of FoxQ1 protein in luminal‐type human breast cancer tissue microarrays when compared with normal mammary tissues. Many previously reported transcriptional targets of FoxQ1 (eg, E‐cadherin, N‐cadherin, fibronectin 1, etc) were verified from the RNA‐seq analysis. FoxQ1 overexpression resulted in the downregulation of genes associated with cell cycle checkpoints, M phase, and cellular response to stress/external stimuli as evidenced from the Reactome pathway analysis. Consequently, FoxQ1 overexpression resulted in mitotic arrest in basal‐like SUM159 and human mammary epithelial cell line, but not in luminal‐type MCF‐7 cells. Finally, we show for the first time that FoxQ1 is a direct transcriptional regulator of interleukin (IL)‐1α, IL‐8, and vascular endothelial growth factor in breast cancer cells as evidenced by chromatin immunoprecipitation assay. In conclusion, the present study reports novel mechanistic targets of FoxQ1 in human breast cancer cells.

中文翻译：

---

人乳腺癌细胞中叉头盒 Q1 转录因子的新机制靶点。

转录因子叉头盒 Q1 (FoxQ1) 在包括乳腺癌在内的不同实体瘤中过度表达，但其致癌功能的机制仍未完全了解。在这项研究中，我们将 FoxQ1 过表达 SUM159 细胞的 RNA-seq 数据与空载体转染的对照细胞的 RNA-seq 数据进行比较，以确定该转录因子的新机制目标。癌症基因组图谱 (TCGA) 数据集的分析显示，与患有该疾病的白人女性相比，黑人乳腺癌患者中FoxQ1 的表达显着更高。相反，FoxQ1 的表达在乳腺癌 TCGA 数据集中的导管癌和小叶癌中具有可比性。补充我们在基底样亚型中发表的研究结果，免疫组织化学揭示了与正常乳腺组织相比，腔型人乳腺癌组织微阵列中 FoxQ1 蛋白的上调。许多先前报道的 FoxQ1 转录靶点（例如，E-钙粘蛋白、N-钙粘蛋白、纤连蛋白 1等）从 RNA-seq 分析中得到验证。如反应组通路分析所证明的，FoxQ1 过表达导致与细胞周期检查点、M 期和细胞对压力/外部刺激的反应相关的基因下调。因此，FoxQ1 过表达导致基底样 SUM159 和人乳腺上皮细胞系有丝分裂停滞，但不会导致管腔型 MCF-7 细胞的有丝分裂停滞。最后，我们首次表明 FoxQ1 是白细胞介素( IL ) -1α、IL-8和血管内皮生长因子的直接转录调节因子染色质免疫沉淀试验证明在乳腺癌细胞中。总之，本研究报告了 FoxQ1 在人乳腺癌细胞中的新机制靶点。