Hippo信号通路核心分子TAZ在卵巢癌中的表达及其作用机制  

Expression of TAZ,a core molecule of the Hippo pathway,in ovarian cancer and its functional mechanisms

作　　者：芦娇娇 李旭[2] 周园园 LU Jiaojiao;LI Xu;ZHOU Yuanyuan(Department of Radiology,First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Center for Translational Medicine,First Affiliated Hospital of Xi'an Jiaotong University;Department of Pathology,First Affiliated Hospital of Xi'an Jiaotong University)

机构地区：[1]西安交通大学第一附属医院医学影像科,西安710061 [2]西安交通大学第一附属医院转化医学中心 [3]西安交通大学第一附属医院病理科

出　　处：《山西医科大学学报》2025年第1期1-7,共7页Journal of Shanxi Medical University

基　　金：国家自然科学基金青年科学基金项目(82203388);西安交通大学第一附属医院院基金项目(2020QN-27)。

摘　　要：目的 探讨基于PDZ结合基序的转录共激活因子(transcriptional coactivator with PDZ-binding motif, TAZ)在卵巢癌中的表达情况,并进一步分析其在卵巢癌中的作用机制。方法 利用仙桃学术分析癌症基因组图谱(The Cancer Genome Atlas, TCGA)数据库中卵巢癌组织及正常对照组织中TAZ mRNA表达水平,并进行受试者工作特征曲线(receiver operating characteristic, ROC)分析。通过人类蛋白质图谱(The Human Protein Atlas, HPA)数据库提供的免疫组化切片,分析TAZ蛋白在卵巢癌组织及正常对照组织中的表达。将卵巢癌细胞SKOV3分为2组:阴性对照组和缺氧组,采用实时定量PCR和Western blot分别检测TAZ的mRNA及蛋白表达;在HIF-2α过表达质粒转染SKOV3细胞后,检测TAZ的表达变化。获取TCGA数据库中376例卵巢癌RNAseq数据及相应的临床信息,通过基因本体论(gene ontology,GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析TAZ相关的差异表达基因,并分析TAZ高、低表达组中铁死亡相关基因的表达差异。结果 卵巢癌中Hippo通路核心分子TAZ的mRNA水平显著下调(P<0.05),蛋白水平上调,TAZ在卵巢癌诊断中的曲线下面积为0.739。与对照组比较,缺氧组SKOV3细胞中TAZ的表达水平显著升高(P<0.05)。转染HIF-2α过表达质粒后,TAZ的mRNA和蛋白表达水平均显著上调(P<0.05)。富集分析结果显示,TAZ可能参与细胞外基质-受体相互作用、局灶黏附、PI3K-Akt信号通路、胶原纤维结构等信号通路及生物学过程。此外,部分铁死亡相关基因的表达在TAZ高、低表达组间存在显著差异。结论 TAZ在卵巢癌中呈现异常表达,并与缺氧反应及铁死亡等关键生物过程密切相关,提示其作为卵巢癌潜在生物标志物和治疗靶点的可能性。Objective To investigate the expression of transcriptional coactivator with PDZ-binding motif(TAZ),a core molecule of Hippo signaling pathway,in ovarian cancer and its potential mechanisms.Methods The mRNA expression levels of TAZ in ovarian cancer tissues and normal control tissues were analyzed using data from The Cancer Genome Atlas(TCGA)database by Xiantao(https://www.xiantao.love/).In addition,receiver operating characteristic(ROC)analysis was performed to assess its diagnostic value.The expression of TAZ protein in ovarian cancer tissues and normal control tissues was detected using immunohistochemical sections provided by The Human Protein Atlas(HPA)database.Ovarian cancer cells SKOV3 were divided into negative control group and hy-poxia group,and the mRNA and protein expression levels of TAZ were detected by quantitative real-time PCR and Western blot,re-spectively.After transfection with a HIF-2αoverexpression plasmid,TAZ expression was detected in SKOV3 cells.RNA-seq data from 376 ovarian cancer patients and their corresponding clinical information in TCGA were used to perform gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of differentially expressed genes associated with TAZ,and the ex-pressions of ferroptosis-related genes were compared between high-and low-TAZ expression groups.Results The mRNA level of TAZ was significantly downregulated in ovarian cancer(P<0.05),while the protein expression of TAZ was upregulated.The area under the ROC curve(AUC)for TAZ in diagnosis of ovarian cancer was 0.739.Compared with control group,the expression of TAZ was sig-nificantly increased in hypoxia group(P<0.05).After overexpression of HIF-2α,TAZ mRNA and protein levels were significantly up-regulated(P<0.05).Enrichment analysis revealed that TAZ might be involved in extracellular matrix-receptor interactions,focal adhe-sion,the PI3K-Akt signaling pathway,and collagen fiber structure,and so on.Additionally,the expression of several ferroptosis-related genes exhibited signifi

关 键 词：卵巢癌 Hippo信号通路 TAZ 生物信息学 细胞缺氧 铁死亡 

分 类 号：R737.31[医药卫生—肿瘤]