实用医学杂志2025，Vol.41Issue(20)：3175-3184,10.DOI:10.3969/j.issn.1006-5725.2025.20.005
微管蛋白2A在肝细胞癌中的表达及其在缺氧条件下对肝癌细胞恶性生物学行为的影响
The expression of TUBB2A in HCC and its effect on malignant biological behaviors of HCC cells under hypoxia
摘要
Abstract
Objective This study aimed to investigate the expression and prognostic significance of Tubulin Beta 2A Class IIa(TUBB2A)in hepatocellular carcinoma(HCC)and to explore its roles in modulating malignant behavior of HCC cells under hypoxia.Methods The expression of TUBB2A in HCC tissues and its correlation with patient prognosis were analyzed using data from The Cancer Genome Atlas Program(TCGA)and validated by Real-time quantitative PCR(qPCR).HepG2 and Hep3B cells were cultured under both normoxia and hypoxia,and followed by assessment of mRNA and protein levels of TUBB2A by qPCR and Western blot.Stable TUBB2A overexpressing and knockout cell models(HepG2 and Hep3B)were established using lentiviral infection technology.The biological function of TUBB2A in HCC cell proliferation,mobility,and invasion of HCC cells under hypoxia were assessed by CCK-8 assay,colony formation assay,and Transwell migration and invasion assays.Western blot was performed to examine the impact of TUBB2A on the expression of key glycolytic proteins,including glucose transporter 1(GLUT1),pyruvate kinase M2(PKM2),and lactate dehydrogenase A(LDHA)in HCC cells under hypoxia.Results TCGA analysis revealed that TUBB2A expression is highly upregulated in HCC tissues compared to that in adjacent tissues and TUBB2A expression is associated with poorer overall survival(P<0.01).The mRNA expression of TUBB2A in HCC tissues from 30 HCC patients was higher than that in corresponding adjacent tissues,and TUBB2A expression is positively associated with the Ⅰ and Ⅳ clinic stage and AFP level of HCC patients(P<0.05).Hypoxia significantly increased TUBB2A mRNA and protein expression in HepG2 and Hep3B cells.Functional studies demonstrated that TUBB2A overexpression under hypoxia enhanced HCC cells proliferation,mobility and invasion,as well as increased the expression of GLUT1、PKM2 and LDHA(P<0.05 or P<0.01).On the contrary,TUBB2A knockout under hypoxia showed opposite effects,suppressed these malignant phenotypes and downregulated glycolytic markers(P<0.05 or P<0.01).Conclusions TUBB2A is significantly overexpressed in HCC and it is closely associated with poor prognosis.Our findings demonstrated that TUBB2A promotes proliferation,migration,invasion and glycolysis in HCC cells under hypoxia,suggesting its potential as a prognostic biomarker and therapeutic target of HCC.关键词
TUBB2A/肝细胞癌/缺氧/增殖与转移/有氧糖酵解Key words
TUBB2A/hepatocellular carcinoma/hypoxia/proliferation and metastasis/glycolysis分类
医药卫生引用本文复制引用
杨伟,梁念孩,夏会东,摆茹..微管蛋白2A在肝细胞癌中的表达及其在缺氧条件下对肝癌细胞恶性生物学行为的影响[J].实用医学杂志,2025,41(20):3175-3184,10.基金项目
宁夏自然科学基金项目(编号:2023AAC03721) （编号:2023AAC03721）
