GTF2 E2通过调控PolⅡ和TFⅡH的活性对子宫内膜癌细胞增殖和侵袭的影响OA

Objective:To investigate the expression profile and functional mechanisms of general transcription factor ⅡE subunit β(GTF2E2)in endometrial carcinoma(EC).Methods:Clinical and transcriptomic data of the Cancer Genome Atlas—the Uterine Corpus Endometrial Carcinoma(TCGA-UCEC)cohort were retrieved and normalized for analysis.Lentivirus-mediated shRNA was used to knockdown GTF2E2 expression.Cell prolifera-tion,migration,invasion,and cell cycle changes of the two groups(shGTF2E2 group and shCtrl group)were de-tected by CCK-8,scratch healing,Transwell invasion and flow cytometry,respectively.A subcutaneous xenograft mouse model was used to assess tumor growth in vivo.Western blotting was employed to determine the protein expression levels of key components of the transcription initiation complex—RNA polymeraseⅡC(PolⅡ)-termi-nal domain kinase(CTD kinase),transcription factor ⅡH DNA-dependent ATPase(TFⅡH-DNA-ATPase)-Along with the downstream effector ribosomal protein S4 X-linked(RPS4X).Results:①TCGA analysis revealed that GTF2E2 was significantly over expressed in EC tissues(P<0.001),whereas its expression level was not signifi-cantly associated with overall survival(P>0.05).②In vitro,GTF2E2 silencing markedly inhibited EC cell prolifera-tion,migration,and invasion,and induced G1-phase cell cycle arrest(P<0.01).Mechanistically,GTF2E2 knock-down downregulated CTD kinase,TFⅡH-DNA-ATPase,and RPS4X protein expression(P<0.001).③Animal ex-periments,tumor volume and weight in the shGTF2E2 group were significantly reduced compared with the shCtrl group(P<0.01).Conclusions:GTF2E2 is highly expressed in EC and promotes tumor cell proliferation and inva-sion,potentially by regulating key transcription initiation complex proteins(CTD kinase and TFⅡH-DNA-ATPase)and the downstream effector RPS4X.GTF2E2 may serve as a potential biomarker for early diagnosis and a novel therapeutic target in EC.