FOXS1通过上调结直肠癌中的CXCL8促进肿瘤进展。
FOXS1 Promotes Tumor Progression by Upregulating CXCL8 in Colorectal Cancer.
作者信息
Qiu Junfeng, Li Mingzhou, Su Cailin, Liang Yihao, Ou Ruizhang, Chen Xiaoning, Huang Chengmei, Zhang Yaxin, Ye Yaping, Liao Wenting, Zhang Chao
机构信息
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
出版信息
Front Oncol. 2022 Jul 8;12:894043. doi: 10.3389/fonc.2022.894043. eCollection 2022.
BACKGROUND
Forkhead box S1 (FOXS1) is a member of the forkhead box (FOX) transcriptional factor superfamily. The biological roles and underlying regulatory mechanism of FOXS1 in CRC remain unclear.
METHODS
Bioinformatics analysis, Western blotting, real-time PCR, and immunohistochemistry (IHC) were used to detect the expression FOXS1 in CRC. MTT assay, transwell assay, human umbilical vein endothelial cell tube formation assay, and chicken chorioallantoic membrane assay were performed to investigate the effects of FOXS1 on proliferation, invasion, and angiogenesis. Additionally, tumor formation assay and orthotopic implantation assay were used to investigate the effects of FOXS1 on tumor growth and metastasis . Furthermore, gene set enrichment analysis (GSEA) was used to analyze the correlation between FOXS1 and EMT or angiogenesis. The correlation between FOXS1 and CXCL8 expression was analyzed in clinical CRC samples using IHC.
RESULTS
The results showed that FOXS1 expression was upregulated in CRC tissues compared with adjacent normal intestine tissues. A high FOXS1 expression is positively correlated with poor survival. FOXS1 promoted the malignant behavior of CRC cancer cells , including proliferation, invasion, and angiogenesis. In addition, FOXS1 promoted tumor growth and metastasis in nude mice. Mechanistically, FOXS1 upregulated the expression of C-X-C motif chemokine ligand 8 (CXCL8) at the transcriptional level. Knockdown of CXCL8 blocked FOXS1 induced the enhancement of the EMT and angiogenesis. GSEAs in public CRC datasets revealed strong correlations between FOXS1 expression and EMT marker and angiogenesis markers. IHC showed that FOXS1 expression was positively correlated with CXCL8 expression and CD31 expression in clinical CRC samples.
CONCLUSION
The results suggest that FOXS1 promotes angiogenesis and metastasis by upregulating CXCL8 in CRC. Interference with the FOXS1/CXCL8 axis may serve as a potential therapeutic target for the treatment of metastatic CRC.
背景
叉头框S1（FOXS1）是叉头框（FOX）转录因子超家族的成员。FOXS1在结直肠癌（CRC）中的生物学作用及潜在调控机制仍不清楚。
方法
采用生物信息学分析、蛋白质免疫印迹法、实时定量聚合酶链反应及免疫组织化学（IHC）检测CRC中FOXS1的表达。进行MTT法、Transwell法、人脐静脉内皮细胞管腔形成实验及鸡胚绒毛尿囊膜实验，以研究FOXS1对增殖、侵袭及血管生成的影响。此外，采用肿瘤形成实验及原位植入实验研究FOXS1对肿瘤生长和转移的影响。进一步地，运用基因集富集分析（GSEA）分析FOXS1与上皮-间质转化（EMT）或血管生成之间的相关性。使用IHC分析临床CRC样本中FOXS1与CXC趋化因子配体8（CXCL8）表达之间的相关性。
结果
结果显示，与相邻正常肠组织相比，CRC组织中FOXS1表达上调。FOXS1高表达与较差的生存率呈正相关。FOXS1促进CRC癌细胞的恶性行为，包括增殖、侵袭及血管生成。此外，FOXS1促进裸鼠肿瘤生长和转移。机制上，FOXS1在转录水平上调CXC基序趋化因子配体8（CXCL8）的表达。敲低CXCL8可阻断FOXS1诱导的EMT及血管生成增强。公共CRC数据集中的GSEA显示FOXS1表达与EMT标志物及血管生成标志物之间存在强相关性。IHC显示，临床CRC样本中FOXS1表达与CXCL8表达及CD31表达呈正相关。
结论
结果表明，FOXS1通过上调CRC中的CXCL8促进血管生成和转移。干扰FOXS1/CXCL8轴可能成为转移性CRC治疗的潜在靶点。
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