FOXM1c promotes oesophageal cancer metastasis by transcriptionally regulating IRF1 expression
FOXM1c promotes oesophageal cancer metastasis by transcriptionally regulating IRF1 expression
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FOXM1c通过转录调节IRF1表达促进食管癌转移
DOI：
10.1111/cpr.12553
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发表时间：
2018
影响因子：
8.5
通讯作者：
Hu W
中科院分区：
文献类型：
--
作者：
Zhou Y;Wang Q;Chu L;Dai W;Zhang X;Chen J;Zhang L;Ding P;Zhang X;Gu H;Zhang P;Li L;Zhang W;Li L;Lv X;Zhou D;Cai G;Chen L;Zhao K;Hu W
目的探讨FOXM1在食管鳞状细胞癌（ESCC）转移中的作用及其分子机制，探讨FOXM1在ESCC中的临床意义。接下来，使用过表达和RNA干扰系统以及transwell进行遗传修饰来检测FOXM 1c在入侵和迁移中的功能。进行双荧光素酶和ChIP测定以解读转录调控的潜在机制。FOXM1和IRF1的表达水平通过免疫组化染色在ESCC samples.ResultsThe FOXM1c主要是过度表达的ESCC细胞系相比，其他FOXM1亚型。FOXM1c的异位表达促进了食管鳞癌细胞系的侵袭和迁移，而FOXM1c的下调抑制了这些过程。此外，FOXM1c的表达与IRF1在ESCC细胞系和肿瘤标本中的表达呈正相关。IRF1至少部分负责FOXM1c介导的侵袭和迁移。从机制上讲，我们将IRF1鉴定为FOXM1c的转录靶点，并在IRF1启动子区域发现了FOXM1c结合位点。结论FOXM1c通过转录靶向IRF1促进食管癌的转移，可作为食管癌患者预后的预测因子。
ObjectivesWe aimed to elucidate the role and molecular mechanisms of FOXM1 in regulating metastasis in oesophageal squamous cell carcinoma (ESCC) as well as its clinical implications.Materials and methodsThe expression levels of four isoforms of FOXM1 were analysed by real‐time PCR. Next, genetically modification using overexpression and RNAi systems and transwell were employed to examine FOXM1c function in invasion and migration. Dual luciferase and ChIP assays were performed to decipher the underlying mechanism for transcriptional regulation. The expression levels of FOXM1 and IRF1 were determined by immunohistochemistry staining in ESCC specimens.ResultsThe FOXM1c was predominantly overexpressed in ESCC cell lines compared to the other FOXM1 isoforms. Ectopic expression of FOXM1c promoted invasion and migration of ESCC cells lines, whereas downregulation of FOXM1c inhibited these processes. Moreover, FOXM1c expression was positively correlated with IRF1 expression in ESCC cell lines and tumour specimens. IRF1 is, at least in part, responsible for FOXM1c‐mediated invasion and migration. Mechanistically, we identified IRF1 as a transcriptional target of FOXM1c and found a FOXM1c‐binding site in the IRF1 promoter region. Furthermore, high expression levels of both FOXM1c and IRF1 were positively associated with low survival rate and predicted a poor prognosis of oesophageal cancer patients.ConclusionFOXM1c promotes the metastasis by transcriptionally targeting IRF1 and may serve as a potential prognostic predictor for oesophageal cancer.