HOXC6通过激活SFRP1/Wnt/β-catenin信号通路促进前列腺癌进展的机制研究  

Mechanism of HOXC6 promoting the progression of prostate cancer by activating the SFRP1/Wnt/β-catenin signaling pathway

作　　者：郑勇军 李文敏[1] 郑立传 周燕峰[1] 王健[1] 夏维木[1] 叶惟靖[2] 俞家顺 ZHENG Yong-jun;LI Wen-min;ZHENG Li-chuan;ZHOU Yan-feng;WANG Jian;XIA Wei-mu;YE Wei-jing;YU Jia-shun(Department of Urology,Punan Hospital of Shanghai Pudong New Area,Shanghai 200125,China;Department of Urology,Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200125,China)

机构地区：[1]上海市浦东新区浦南医院泌尿外科,上海200125 [2]上海交通大学医学院附属仁济医院泌尿科,上海200125

出　　处：《中华男科学杂志》2024年第7期579-587,共9页National Journal of Andrology

基　　金：上海市浦东新区卫生系统学科带头人培养计划(PWRd2022-07);上海市浦东新区乳糜疾病特色专病(PWZb2022-07)。

摘　　要：目的:探讨同源盒家族中的人类同源盒C6(HOXC6)基因在前列腺癌中的表达情况及其对前列腺癌细胞增殖、侵袭和迁移能力的影响及机制。方法:应用基于基因表达水平值的交互式分析平台(GEPIA)数据库中关于HOXC6研究的数据,对其在前列腺癌中的表达水平变化进行分析。采用GEPIA数据库分析HOXC6表达水平与前列腺癌患者生存预后之间的关系。通过Western印迹检测HOXC6蛋白在前列腺癌组织、正常前列腺组织及不同前列腺癌细胞株DU-145、PC-3以及正常人前列腺上皮细胞RWPE-1中的表达情况。在人前列腺癌细胞DU145、PC-3和正常人前列腺上皮细胞RWPE-1中,利用siRNA质粒稳定干扰HOXC6基因表达,采用CCK8、平板克隆、划痕、Transwell侵袭实验检测HOXC6基因对前列腺癌细胞增殖、迁移、侵袭能力的影响。通过GEPIA数据库分析Wnt抑癌因子分泌型卷曲相关蛋白1(SFRP1)基因与HOXC6的相关性,采用Western印迹检测HOXC6-siRNA转染后PC-3细胞中HOXC6、SFRP1、Wnt及β-catenin蛋白表达。结果:HOXC6在前列腺癌组织中的表达高于正常前列腺组织(P<0.01),在前列腺癌细胞中的表达高于正常前列腺上皮细胞(P<0.01)。结合生物信息学分析,HOXC6高表达的PCa患者比低表达的生存率低(P=0.011)。siRNA组HOXC6蛋白相对表达量、吸光度值、克隆形成数、侵袭细胞数低于阴性对照组,差异有统计学意义(P<0.05)。通过GEPIA数据库发现SFRP1高表达的前列腺癌患者预后较好,在体外实验中,前列腺癌PC-3细胞系中,Western印迹分析Wnt及β-catenin蛋白的表达均上升,SFRP1蛋白表达明显下降(P<0.05);与siRNA-NC、前列腺癌PC-3相比,siRNA-HOXC6转染组中的Wnt及β-catenin蛋白的表达均明显下降,SFRP1蛋白表达上升(P<0.05)。结论:HOXC6在前列腺癌组织中高表达,并与前列腺癌细胞的增殖、迁移和侵袭有关;HOXC6通过抑制SFRP1/Wnt/β-catenin信号通路从而促进前列腺癌DU145、PC-3细�Objective:To study the expression of the Homeobox C6(HOXC6)gene in the homeobox family in PCa,its effect on the biological behavior of PCa cells and its action mechanism.Methods:Based on the studies of HOXC6 retrieved from the database of Gene Expression Profiling Interactive Analysis(GEPIA),we analyzed the expression of HOXC6 in PCa and the relationship of its expression level with the survival prognosis of the patients.We detected the expression of the HOXC6 protein in PCa tissues and cells by Western blot,stably interfered with the expression of the HOXC6 gene in human PCa DU145 and PC-3 cells and normal prostatic epithelial RWPE-1 cells using the siRNA plasmid,and determined the effects of HOXC6 on the proliferation,migration and invasiveness of PCa cells by CCK8,plate cloning and scratch healing and Transwell invasion assays.Using the GEPIA database,we analyzed the correlation of the Wnt tumor inhibitory factor-secreted frizzled-related protein 1(SFRP1)gene with HOXC6,and detected the expressions of HOXC6,SFRP1,Wnt andβ-catenin in PC-3 cells after siRNA-HOXC6 transfection by Western blot.Results:The expression of HOXC6 was dramatically higher in the PCa than in the normal prostate tissue(P<0.01),and in the PCa cells than in the normal prostatic epithelial cells(P<0.01).Bioinformatics analysis indicated a lower survival rate of the PCa patients with a high than those with a low HOXC6 expression(P=0.011).The relative expression of the HOXC6 protein,absorbance value,number of clones formed and number of invaded cells were significantly lower in the siRNA group than in the negative controls(P<0.05).According to the GEPIA database,highly expressed SFRP1 was associated with a good prognosis of PCa,and the protein expressions of Wnt andβ-catenin were markedly increased while that of SFRP1 decreased in the PCa PC-3 cell line(P<0.05).The expressions of the Wnt andβ-catenin proteins were decreased and that of SFRP1 increased significantly in the siRNA-HOXC6 transfection group compared with those in the siRNA negati

关 键 词：前列腺癌 HOXC6 SFRP1/Wnt通路 增殖 迁移 侵袭 

分 类 号：R737.25[医药卫生—肿瘤]