ATL3在肝细胞癌中的作用及机制初探  

Preliminary exploration on the role of ATL3 in hepatocellular carcinoma and its potential mechanism

作　　者：袁建辉 张辰轩 张馨 董可帅 李满[1] 余佳[1] YUAN Jianhui;ZHANG Chenxuan;ZHANG Xin;DONF Keshuai;LI Man;YU Jia(Department of Hepatobiliary Surgery,People’s Hospital of Wuhan University,Wuhan,Hubei 40060,China)

机构地区：[1]武汉大学人民医院肝胆外科,湖北武汉430060

出　　处：《肝胆胰外科杂志》2025年第3期191-199,共9页Journal of Hepatopancreatobiliary Surgery

基　　金：湖北省自然科学基金(2023AFB197)。

摘　　要：目的探讨ATLASTINS3(ATL3)在肝细胞癌(HCC)中的作用和潜在机制。方法收集85例HCC患者组织标本,通过免疫组化及Western blotting实验检测肝癌组织与癌旁正常组织中ATL3的表达水平并分析其与HCC患者临床预后的关系;通过质粒转染敲减以及过表达肝癌细胞系中的ATL3基因,通过Western blotting实验检测敲减及过表达后ATL3及相关蛋白的变化;通过细胞增殖实验、Edu实验检测ATL3不同表达水平对肝癌细胞增殖能力的影响;通过Transwell实验及细胞划痕实验检测ATL3敲减或过表达后对肿瘤细胞迁移和侵袭能力的影响;通过裸鼠皮下成瘤实验,检测ATL3在体内对肿瘤生长的影响。结果ATL3在肝癌组织中表达较高,对临床资料分析显示ATL3的表达与ALT(P=0.003)、AST(P=0.048)、Child-Pugh分级(P=0.020)、血管侵犯(P<0.001)、肿瘤分化程度(P=0.047)以及Edmonson分期(P=0.001)显著有关;细胞实验结果显示,ATL3敲低后细胞增殖能力、侵袭与迁移能力都有所下降,过表达ATL3后肝癌细胞增殖能力、侵袭与迁移能力均呈现增强趋势;在过表达ATL3的肝癌细胞中PI3K、p-PI3K、AKT、p-AKT的蛋白表达升高,敲减ATL3的细胞中PI3K、p-PI3K、AKT、p-AKT的表达则降低。裸鼠皮下成瘤实验结果显示,ATL3敲减后皮下瘤的质量(P=0.005)以及体积(P=0.006)均明显低于野生型对照组。结论ATL3在HCC中高表达,其高表达与患者不良预后相关;ATL3可能通过促进PI3K/AKT通路激活发挥促癌作用。Objective To investigate the role of ATLASTIN3(ATL3)in hepatocellular carcinoma(HCC)and its potential mechanism.Methods HCC tissue and paracancerous tissue samples of 85 patients were collected to analyze ATL3 expression in tumor and paracancerous tissues by immunohistochemistry and Western blotting.The correlation between ATL3 expression levels and the clinical features and prognosis of HCC patients were evaluated.ATL3 was knocked-down or overexpressed through plasmid transfection in liver carcinoma cell lines,and subsequent changes in ATL3 and related protein levels were examined by Western blotting.The eff ects of altered ATL3 expression on HCC cell proliferation were assessed by cell proliferation assays and EdU assays.Cell migration and invasion were investigated by Transwell and wound-healing assays.The eff ect of ATL3 on tumor growth in vivo was detected by subcutaneous tumor formation assay in nude mice.Results ATL3 was highly expressed in HCC tissues.Clinical analysis revealed that,ATL3 expression was associated with ALT(P=0.003),AST(P=0.048),Child-Pugh grade(P=0.020),vascular invasion(P<0.001),tumor differentiation(P=0.047)and Edmonson stage(P=0.001).In vitro experiments demonstrated that,ATL3 knockdown leaded to decreased cell proliferation,invasion and migration,while overexpression of ATL3 enhanced these abilities in HCC cells.Furthermore,protein expression levels of PI3K,p-PI3K,AKT,and p-AKT were elevated in ATL3-overexpressed HCC cells,whereas their levels were reduced in ATL3-knockdown cells.Subcutaneous tumorigenesis experiments in nude mice showed that,compared with the wild-type control group,tumors with ATL3 knockdown exhibited significantly lower weight(P=0.005)and volume(P=0.006).Conclusion ATL3 is overexpressed in HCC and correlates with poor prognosis of HCC patients.ATL3 may promote cancer progression by activating the PI3K/AKT pathway.

关 键 词：肝细胞癌 ATL3 PI3K/AKT信号通路 裸鼠成瘤 临床预后分析 

分 类 号：R735.7[医药卫生—肿瘤]