Zhang Jing, Liu Yimin, Zhang Jia, Cui Xiaohai, Li Gang, Wang Jiansheng, Ren Hong, Zhang Yunfeng
The Second Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Baoji Renmin Hospital, Baoji, Shaanxi 721000, P.R. China.
Oncol Rep. 2016 Jun;35(6):3607-13. doi: 10.3892/or.2016.4736. Epub 2016 Apr 8.
Gastric cancer (GC) is one of the most common cancers, and the second most common cause of cancer deaths worldwide. Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family and its upregulation is closely correlated with tumor progression and prognosis of multiple cancer types, including GC. FOXQ1 has been shown to regulate EMT and function in human cancers. However, the role of FOXQ1 in regulating EMT in GC and the exactly mechanism has not been clarified. The purpose of this study was to investigate the effects of FOXQ1 on EMT in human GC. FOXQ1 protein was detected by immunohistochemistry in human GC specimens and their clinical significance evaluated. We examined the cell biology and molecular biology changes after overexpression and knockdown of FOXQ1 in gastric cancer cells in vitro. To further understand the underlying mechanisms of EMT promoted by FOXQ1, we examined the changes of target genes of FOXQ1 after overexpression and knockdown of FOXQ1 in gastric cancer cells. In the present study, we demonstrate that FOXQ1 is overexpressed in GC tissues and its expression level is closely correlated with histologic differentiation, pTNM stage, and lymphatic metastasis of GC. Kaplan-Meier survival analysis showed that a high expression level of FOXQ1 resulted in a significantly poor prognosis of GC patients. FOXQ1 modulated GC cell invasion in vitro, and induced E-cadherin repression. FOXQ1 also upregulated the expression of vimentin in vitro. The Snail signaling pathway was likely involved in the induction of EMT by FOXQ1 in GC. Our results demonstrate that FOXQ1 is a prognostic marker for patients with GC, FOXQ1 over-expression is involved in acquisition of the mesenchymal phenotype of gastric cancer cells, and that subsequent Snail expression is essential for induction of EMT. The results suggest that FOXQ1 is a potential therapeutic target for the development of therapies for GC.
胃癌（GC）是最常见的癌症之一，也是全球癌症死亡的第二大常见原因。叉头框Q1（FOXQ1）是叉头转录因子家族的成员，其上调与包括GC在内的多种癌症类型的肿瘤进展和预后密切相关。FOXQ1已被证明在人类癌症中调节上皮-间质转化（EMT）并发挥作用。然而，FOXQ1在GC中调节EMT的作用及确切机制尚未阐明。本研究的目的是探讨FOXQ1对人GC中EMT的影响。通过免疫组织化学检测人GC标本中的FOXQ1蛋白，并评估其临床意义。我们在体外检测了胃癌细胞中FOXQ1过表达和敲低后细胞生物学和分子生物学的变化。为了进一步了解FOXQ1促进EMT的潜在机制，我们检测了胃癌细胞中FOXQ1过表达和敲低后FOXQ1靶基因的变化。在本研究中，我们证明FOXQ1在GC组织中过表达，其表达水平与GC的组织学分化、pTNM分期和淋巴转移密切相关。Kaplan-Meier生存分析表明，FOXQ1高表达导致GC患者预后显著不良。FOXQ1在体外调节GC细胞侵袭，并诱导E-钙黏蛋白表达下调。FOXQ1在体外还上调波形蛋白的表达。Snail信号通路可能参与了FOXQ1在GC中诱导的EMT。我们的结果表明，FOXQ1是GC患者的预后标志物，FOXQ1过表达参与了胃癌细胞间充质表型的获得，并且随后Snail表达对于诱导EMT至关重要。结果表明，FOXQ1是GC治疗开发的潜在治疗靶点。
