PDF(Pubmed)
Abstract：
The improvements in the treatment of colorectal cancer (CRC) and prolongation of survival time have improved the incidence of bone metastasis. Forkhead box D3 (FOXD3) is involved in the development of CRC. However, the role and mechanism of FOXD3 in CRC bone metastases development are unknown.
Using the combined bioinformatics and cytology experimental analyses, this study aimed to explore the mechanistic role of FOXD3 in the bone metastasis of colon cancer, thereby aiding in the treatment of colon cancer bone metastasis and identification of drug-targeting markers.
First, the changes in the expression levels of the FOXD3 gene and differentially expressed genes (DEGs) between the colon cancer samples and colon cancer metastases were obtained from The Cancer Genome Atlas (TCGA) database. Then, the correlations of the FOXD3 gene with the DEGs were identified. Next, the effects of the FOXD3 on the proliferation and invasion abilities of colon cancer bone metastatic cells were identified using Cell Counting Kit-8 (CCK8) and Transwell cell migration assays, respectively. In addition, Western blot analysis was used to identify the expression levels of the proteins related to the EGFR/Ras/Raf/MEK/ERK (EGFR/ERK) signaling pathway and epithelial-to-mesenchymal transition (EMT).
FOXD3 was downregulated in colon cancer and could interact with multiple DEGs in colon cancer bone metastases. FOXD3 gene knockdown could increase the proliferation of human colon cancer bone metastatic cells and their invasive ability. FOXD3 gene knockdown could activate the expression of EGFR/ERK signaling pathway-related proteins and inhibit/promote the expression of EMT-related proteins, which in turn promoted the proliferation and metastasis of LoVo cells from colon cancer bone metastases.
Overall, this study demonstrated that the downregulation of the FOXD3 gene might promote the proliferation of colon cancer bone metastatic cell lines through the EGFR/ERK pathway and promote their migration through EMT, thereby serving as a promising therapeutic target.
Using the combined bioinformatics and cytology experimental analyses, this study aimed to explore the mechanistic role of FOXD3 in the bone metastasis of colon cancer, thereby aiding in the treatment of colon cancer bone metastasis and identification of drug-targeting markers.
First, the changes in the expression levels of the FOXD3 gene and differentially expressed genes (DEGs) between the colon cancer samples and colon cancer metastases were obtained from The Cancer Genome Atlas (TCGA) database. Then, the correlations of the FOXD3 gene with the DEGs were identified. Next, the effects of the FOXD3 on the proliferation and invasion abilities of colon cancer bone metastatic cells were identified using Cell Counting Kit-8 (CCK8) and Transwell cell migration assays, respectively. In addition, Western blot analysis was used to identify the expression levels of the proteins related to the EGFR/Ras/Raf/MEK/ERK (EGFR/ERK) signaling pathway and epithelial-to-mesenchymal transition (EMT).
FOXD3 was downregulated in colon cancer and could interact with multiple DEGs in colon cancer bone metastases. FOXD3 gene knockdown could increase the proliferation of human colon cancer bone metastatic cells and their invasive ability. FOXD3 gene knockdown could activate the expression of EGFR/ERK signaling pathway-related proteins and inhibit/promote the expression of EMT-related proteins, which in turn promoted the proliferation and metastasis of LoVo cells from colon cancer bone metastases.
Overall, this study demonstrated that the downregulation of the FOXD3 gene might promote the proliferation of colon cancer bone metastatic cell lines through the EGFR/ERK pathway and promote their migration through EMT, thereby serving as a promising therapeutic target.
摘要：
背景：结直肠癌（CRC）治疗的改善和生存时间的延长改善了骨转移的发生率。叉头盒D3(FOXD3)涉及CRC的开发。然而,FOXD3在CRC骨转移发展中的作用和机制尚不清楚。
目的：结合生物信息学和细胞学实验分析，本研究旨在探讨FOXD3在结肠癌骨转移中的作用机制,从而有助于结肠癌骨转移的治疗和药物靶向标志物的鉴定。
方法：首先，从癌症基因组图谱(TCGA)数据库获得结肠癌样本和结肠癌转移灶之间FOXD3基因和差异表达基因(DEGs)表达水平的变化.然后，鉴定了FOXD3基因与DEGs的相关性。接下来,使用细胞计数Kit-8（CCK8）和Transwell细胞迁移试验鉴定FOXD3对结肠癌骨转移细胞增殖和侵袭能力的影响，分别。此外,蛋白质印迹分析用于鉴定与EGFR/Ras/Raf/MEK/ERK(EGFR/ERK)信号通路和上皮-间质转化(EMT)相关的蛋白的表达水平。
结果：FOXD3在结肠癌中表达下调，并可与结肠癌骨转移中的多个DEGs相互作用。FOXD3基因敲低可增加人结肠癌骨转移细胞的增殖及其侵袭能力。FOXD3基因敲低可以激活EGFR/ERK信号通路相关蛋白的表达,抑制/促进EMT相关蛋白的表达,进而促进结肠癌骨转移瘤LoVo细胞的增殖和转移。
结论：总体而言，这项研究表明，FOXD3基因的下调可能通过EGFR/ERK通路促进结肠癌骨转移细胞系的增殖，并通过EMT促进其迁移，从而作为一个有希望的治疗目标。
目的：结合生物信息学和细胞学实验分析，本研究旨在探讨FOXD3在结肠癌骨转移中的作用机制,从而有助于结肠癌骨转移的治疗和药物靶向标志物的鉴定。
方法：首先，从癌症基因组图谱(TCGA)数据库获得结肠癌样本和结肠癌转移灶之间FOXD3基因和差异表达基因(DEGs)表达水平的变化.然后，鉴定了FOXD3基因与DEGs的相关性。接下来,使用细胞计数Kit-8（CCK8）和Transwell细胞迁移试验鉴定FOXD3对结肠癌骨转移细胞增殖和侵袭能力的影响，分别。此外,蛋白质印迹分析用于鉴定与EGFR/Ras/Raf/MEK/ERK(EGFR/ERK)信号通路和上皮-间质转化(EMT)相关的蛋白的表达水平。
结果：FOXD3在结肠癌中表达下调，并可与结肠癌骨转移中的多个DEGs相互作用。FOXD3基因敲低可增加人结肠癌骨转移细胞的增殖及其侵袭能力。FOXD3基因敲低可以激活EGFR/ERK信号通路相关蛋白的表达,抑制/促进EMT相关蛋白的表达,进而促进结肠癌骨转移瘤LoVo细胞的增殖和转移。
结论：总体而言，这项研究表明，FOXD3基因的下调可能通过EGFR/ERK通路促进结肠癌骨转移细胞系的增殖，并通过EMT促进其迁移，从而作为一个有希望的治疗目标。
