南方医科大学学报2025,Vol.45Issue(12):2628-2638,11.DOI:10.12122/j.issn.1673-4254.2025.12.10
血管相关迁移细胞蛋白在肝细胞癌中高表达并促进肝癌细胞侵袭转移
Angio-associated migratory cell protein is highly expressed in hepatocellular carcinoma and promotes tumor cell invasion and metastasis
摘要
Abstract
Objective To investigate the clinical significance of abnormal expression of angio-associated migratory cell protein(AAMP)in hepatocellular carcinoma(HCC).Methods Bioinformatics analyses were used to analyze AAMP expression level in HCC and its prognosis value.In 60 pairs of HCC and adjacent tissues,AAMP expression was detected immunohistochemically and its correlation with clinicopathological characteristics of the patients was analyzed.In cultured Mahlavu and Huh-7 cells with lentivirus-mediated AAMP knockdown,the changes in cell proliferation,apoptosis,migration and invasion were observed,and their lung metastasis following tail vein injection in nude mice were assessed.In HCC cells with AAMP knockdown,Western blotting,immunofluorescence staining or RT-qPCR were used to examine the changes in expression levels of E-cadherin,N-cadherin,Vimentin and Snail and the effects of MG-132 and CHX on RhoA expression.The correlation between the expressions of AAMP and RhoA in HCC tissues was analyzed by immunohistochemistry.Results Bioinformatics analysis showed that AAMP expression was elevated in HCC tissues(P<0.05)in correlation with advanced clinical stage and poor prognosis(P<0.05).Immunohistochemistry results confirmed significant correlations of high AAMP expression with Edmondson-Steiner grade(III+IV),venous infiltration and TNM stage(III+IV)of HCC(P<0.05).In cultured HCC cells,AAMP knockdown did not significantly affect cell proliferation or apoptosis,but obviously suppressed cell migration and invasion in vitro and lung metastasis in nude mice.AAMP knockdown significantly increased E-cadherin expression,decreased N-cadherin,Vimentin and Snail expressions,and reduced RhoA protein levels without obviously affecting RhoA mRNA levels.MG-132 treatment blocked the inhibitory effect of AAMP knockdown on RhoA protein expression.The expressions of AAMP and RhoA showed a significant positive correlation in HCC tissues(P<0.05).Conclusion AAMP overexpression is associated with malignant clinical features of HCC and promotes epithelial-mesenchymal transition and metastasis of HCC cells partly by stabilizing RhoA expression.关键词
血管相关迁移细胞蛋白/肝细胞癌/上皮间质转化/侵袭/转移/RhoAKey words
angio-associated migratory cell protein/hepatocellular carcinoma/epithelial-mesenchymal tran-sition/invasion/metastasis/RhoA引用本文复制引用
LI Chao,YIN Guozhi,CHENG Xiao,JIANG Yezhen..血管相关迁移细胞蛋白在肝细胞癌中高表达并促进肝癌细胞侵袭转移[J].南方医科大学学报,2025,45(12):2628-2638,11.基金项目
陕西省自然科学基础研究计划资助项目(2021JQ-397) (2021JQ-397)
北京市医院管理中心"青苗人才"计划专项经费资助(QML20210903) (QML20210903)