■食管鳞状细胞癌(ESCC)是一种常见的病理食管癌,预后较差。据报道,维生素D缺乏发生在ESCC患者中,这与维生素D受体(VDR)的单核苷酸多态性有关。
■我们研究了VDR对ESCC增殖的影响,入侵,转移及其潜在机制。
■从20例ESCC患者收集ESCC和正常组织。ESCC组织微阵列包含116对ESCC和正常组织以及73个单个ESCC组织。通过实时定量聚合酶链反应确定VDR的表达及其临床病理作用。蛋白质印迹,和免疫组织化学染色。sh-VDR和VDR过表达验证VDR对ESCC细胞表型的影响,基于串联质量标签的定量蛋白质组学和生物信息学方法鉴定了差异VDR相关蛋白。下游通路和调控效应采用通路分析法(IPA)进行分析。通过平行反应监测和蛋白质印迹验证差异表达的蛋白质。在尾静脉注射VDR缺陷型ESCC细胞后,体内成像显示皮下肿瘤生长。
■在ESCC组织和细胞中观察到高VDR表达。性别,T级,TNM分期与VDR表达有关,是ESCC的独立预后因素。VDR下调抑制ESCC细胞增殖,入侵,和体外迁移以及体内皮下肿瘤生长和肺转移。细胞表型改变在VDR上调后逆转,差异蛋白主要富集在p53信号通路中。TP53与ABCG2、APOE、FTH1,GCLM,GPX1,HMOX1,JUN,PRDX5和SOD2可能激活细胞凋亡和抑制氧化应激,细胞转移,和扩散。TP53在VDR敲低后上调,TP53下调逆转了VDR敲低诱导的细胞表型改变。
■VDR可能抑制p53信号通路的激活并诱导ESCC增殖,入侵,和转移通过激活氧化应激。
UNASSIGNED: Esophageal squamous cell carcinoma (ESCC) is a common pathological esophageal cancer with poor prognosis. Vitamin D deficiency reportedly occurs in ESCC patients, and this is related to single nucleotide polymorphism of vitamin D receptor (VDR).
UNASSIGNED: We investigated the effect of VDR on ESCC proliferation, invasion, and metastasis and its potential mechanism.
UNASSIGNED: ESCC and normal tissues were collected from 20 ESCC patients. The ESCC tissue microarray contained 116 pairs of ESCC and normal tissues and 73 single ESCC tissues. VDR expression and its clinicopathological role were determined by real-time quantitative polymerase chain reaction, Western blot, and immunohistochemistry staining. sh-VDR and VDR overexpression were used to validate the effect of VDR on ESCC cell phenotype, and tandem mass tag-based quantitative proteomics and bioinformatics methods identified differential VDR-related proteins. The downstream pathway and regulatory effect were analyzed using ingenuity pathway analysis (IPA). Differentially expressed proteins were verified through parallel reaction monitoring and Western blot. In vivo imaging visualized subcutaneous tumor growth following tail vein injection of VDR-deficient ESCC cells.
UNASSIGNED: High VDR expression was observed in ESCC tissues and cells. Gender, T stage, and TNM stage were related to VDR expression, which was the independent prognostic factor related to ESCC. VDR downregulation repressed ESCC cell proliferation, invasion, and migration in vitro and subcutaneous tumor growth and lung metastases in vivo. The cell phenotype changes were reversed upon VDR upregulation, and differential proteins were mainly enriched in the p53 signaling pathway. TP53 cooperated with ABCG2, APOE, FTH1, GCLM, GPX1, HMOX1, JUN, PRDX5, and SOD2 and may activate apoptosis and inhibit oxidative stress, cell metastasis, and proliferation. TP53 was upregulated after VDR knockdown, and TP53 downregulation reversed VDR knockdown-induced cell phenotype changes.
UNASSIGNED: VDR may inhibit p53 signaling pathway activation and induce ESCC proliferation, invasion, and metastasis by activating oxidative stress.