TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways  

作　　者：Yan Zhang Zhen-Zhen Wang An-Qi Han Ming-Ya Yang Li-Xin Zhu Fa-Ming Pan Yong Wang 

机构地区：[1]Department of General Surgery,The Second Hospital of Anhui Medical University,Hefei 230601,China [2]Department of General Surgery,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China [3]Department of Epidemiology and Biostatistics,School of Public Health,Anhui Medical University,Hefei 230032,China [4]The Key Laboratory of Major Autoimmune Diseases,Anhui Medical University,Hefei 230032,China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2024年第2期195-209,共15页国际肝胆胰疾病杂志（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(52072005 and 51872279).

摘　　要：Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.

关 键 词：TuBG1 Hepatocellular carcinoma APOPTOSIS Cell cycling IMMUNOMODULATORS 

分 类 号：R735.7[医药卫生—肿瘤]