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ASAP1通过在体外和体内调节Wnt/β-连环蛋白信号通路促进肝外胆管癌进展。

ASAP1 promotes extrahepatic cholangiocarcinoma progression by regulating the Wnt/β-catenin pathway in vitro and in vivo.

作者信息

He Jiaqi, Liu Han, Cai Jianhua, Shen Sheng, Wang Jiwen, Liu Houbao

机构信息

Department of General Surgery, Zhongshan Hospital Affiliated to Fudan University Shanghai 200032, China.

Department of General Surgery, Huadong Hospital Affiliated to Fudan University Shanghai 200040, China.

出版信息

Am J Cancer Res. 2024 Nov 15;14(11):5178-5192. doi: 10.62347/RKQX3504. eCollection 2024.

Abstract

This study sought to identify the relationship between ADP-ribosylation factor GTPase-activating protein (ASAP1) expression and clinical outcomes in extrahepatic cholangiocarcinoma (EHCC) patients. Quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry were used to analyze the expression of ASAP1 in cholangiocarcinoma (CC) tissue samples and cell lines. The survival rate and clinicopathological characteristics of CC patients were also examined. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. Flow cytometry was used to assess the cell cycle distribution. Both and experiments showed that ASAP1 knockdown decreased cell proliferation, inhibited cell cycle progression, and increased apoptosis. ASAP1 regulates Wnt/β-catenin pathway activity in CC, promoting cell migration, and invasion in culture; and promotes tumor development . ASAP1 plays a key role in EHCC tumor development and could serve as a potential therapeutic target for EHCC.

摘要

本研究旨在确定ADP核糖基化因子GTP酶激活蛋白(ASAP1)表达与肝外胆管癌(EHCC)患者临床结局之间的关系。采用定量实时聚合酶链反应(qRT-PCR)、蛋白质免疫印迹法和免疫组织化学法分析ASAP1在胆管癌(CC)组织样本和细胞系中的表达。还检测了CC患者的生存率和临床病理特征。使用细胞计数试剂盒-8(CCK-8)和5-乙炔基-2'-脱氧尿苷(EdU)检测法检测细胞增殖。采用流式细胞术评估细胞周期分布。 和 实验均表明,ASAP1基因敲低可降低细胞增殖、抑制细胞周期进程并增加细胞凋亡。ASAP1调节CC中的Wnt/β-连环蛋白信号通路活性,促进培养中的细胞迁移和侵袭;并促进肿瘤发展。ASAP1在EHCC肿瘤发展中起关键作用,可作为EHCC的潜在治疗靶点。

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