Background:Transcription factor 3(TCF3)plays pivotal roles in embryonic development,stem cell main-tenance and carcinogenesis.However,its role in hepatocellular carcinoma(HCC)remains largely un-known.This study aimed to analyze the correlation between TCF3 expression and clinicopathological features of HCC,and further explore the underlying mechanism in HCC progression.Methods:The expression of TCF3 was collected from the Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO)HCC datasets,and further confirmed by immunostaining and Western blot-ting assays.The correlation between TCF3 expression and the clinicopathological features was evaluated.Bioinformatical analysis and in vitro experiments were conducted to explore the potential role of TCF3 in HCC development.Results:Both the mRNA and protein levels of TCF3 were significantly higher in HCC tumor tissues com-pared to tumor adjacent tissues(P＜0.001 and P＜0.01).Analysis based on TCGA datasets showed that TCF3 was positively correlated with tumor clinical stage and grade,and patients with high TCF3 expres-sion had shorter overall survival(P=0.012),disease-specific survival(P=0.022)and progression-free survival(P=0.013).Similarly,the immunostaining results revealed that the high expression of TCF3 was closely correlated with tumor size(P=0.001)and TNM stage(P=0.002),and TCF3 was an independent risk factor of HCC.In vitro study exhibited that TCF3 knockdown dramatically suppressed cancer cell pro-liferation,and the underlying mechanism might be that the silencing of TCF3 reduced the expression of critical regulating proteins towards cell cycle and proteins involved in Wnt signaling pathways.Conclusions:TCF3 expression is significantly elevated in HCC and positively associated with the tumor size and TNM stage,as well as poor prognosis of HCC patients.The mechanism might be that TCF3 pro-motes cancer cell proliferation via activating Wnt signaling pathway.

Xing-Yu Pu;Dao-Feng Zheng;Tao Lv;Yong-Jie Zhou;Jia-Yin Yang;Li Jiang

Department of Liver Surgery and Liver Transplantation Center,West China Hospital,Sichuan University,Chengdu 610041,China;Laboratory of Liver Transplantation,Frontiers Science Center for Disease-Related Molecular Network,West China Hospital,Sichuan University,Chengdu 610041,China

国际肝胆胰疾病杂志(英文版)

[1]Xing-Yu Pu;Dao-Feng Zheng;Tao Lv;Yong-Jie Zhou;Jia-Yin Yang;Li Jiang-.Overexpression of transcription factor 3 drives hepatocarcinoma development by enhancing cell proliferation via activating Wnt signaling pathway)[J].国际肝胆胰疾病杂志(英文版),2022(04):378-386

Bioinformatical

Overexpression,transcription,drives,hepatocarcinoma,development,by,enhancing,proliferation,via,activating,Wnt,signaling,Background,Transcription,TCF3,plays,pivotal,roles,embryonic,stem,tenance,carcinogenesis,However,its,hepatocellular,HCC,remains,largely,known,This,study,aimed,analyze,correlation,between,clinicopathological,features,further,explore,underlying,mechanism,progression,Methods,was,collected,from,Cancer,Genome,Atlas,TCGA,Gene,Expression,Omnibus,GEO,datasets,confirmed,immunostaining,blot,assays,evaluated,analysis,vitro,experiments,were,conducted,potential,Results,Both,levels,significantly,higher,tumor,tissues,com,pared,adjacent,Analysis,showed,that,positively,correlated,clinical,stage,grade,patients,had,shorter,overall,survival,disease,specific,free,Similarly,results,revealed,closely,size,TNM,independent,risk,In,exhibited,knockdown,dramatically,suppressed,cancer,might,silencing,reduced,critical,regulating,proteins,towards,cycle,involved,pathways,Conclusions,elevated,associated,well,poor,prognosis,motes

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