肝胆胰外科杂志2025,Vol.37Issue(3):191-199,9.DOI:10.11952/j.issn.1007-1954.2025.03.009
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
摘要
Abstract
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 effects 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 effect 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Key words
hepatocellular carcinoma/ATL3/PI3K/AKT pathway/nud mice tumorigenesis/clinical prognosis analysis分类
临床医学引用本文复制引用
袁建辉,张辰轩,张馨,董可帅,李满,余佳..ATL3在肝细胞癌中的作用及机制初探[J].肝胆胰外科杂志,2025,37(3):191-199,9.基金项目
湖北省自然科学基金(2023AFB197). (2023AFB197)