GBP2 and STAT1 Synergistically Regulate the Development of HCC
Objective To investigate the expression of guanylate binding protein 2(GBP2)in hepatocellular carcinoma(HCC)and its effects on HCC.Methods A total of 78 HCC patients(65 males and 13 females)from the Second Affiliated Hospital of Nanchang University were selected for the study,and HCC tumor tissues and paracancerous tissues were extracted.HCC cell lines(SK-HEP-1,HCCLM3,and Huh-7)and normal hepatocytes HL7702 were procured for experiment.Four-week-old male mice were randomly divided into the shGBP2 interference group(n=5)and the shCtrl group(n=5).The expression level of GBP2 in HCC and its relationship with overall survival were analyzed.Short hairpin RNA was employed to achieve stable knockdown of GBP2 in HCC cells,and the most relevant co-expression genes of GBP2 were screened.Their effects on tumor cells were investigated through a series of in vivo and in vitro cell biology experiments.Results The expression level of GBP2 in HCC tissues was significantly higher than that in paracancerous tissues(P＜0.001);GBP2 expression level was positively correlated with HCC stage(P=0.001)and T infiltration(P=0.001);patients with high GBP2 expression had lower survival rates compared to those with low expression(P＜0.001).In the shGBP2 interference group(GBP2 knockout),HCCLM3 and SK-HEP 1 cells exhibited decreased proliferation(P＜0.001),significantly lower mobility(P＜0.001),and increased apoptosis(P＜0.01).Tumor growth in the shGBP2 interference group was slower than that in the shCtrl group(P＜0.001),and the mean tumor weight in the shGBP2 interference group was significantly lower than that in the shCtrl group(P＜0.001).The positive correlation index between the expression of STAT1 and GBP2 was the highest(r=0.248).The expression of STAT1 in HCC tumor cells(HCCLM3,SK-HEP-1)was significantly higher than that in normal hepatocytes HL-7702(P＜0.001).GBP2-overexpressed HCC cells exhibited the lowest apoptosis rate(P＜0.001),while STAT1 knockout cells showed the highest apoptosis rate(P＜0.05).The proliferation ability of HCC cells with low STAT1 knockdown was markedly decreased(P＜0.001).Furthermore,both proliferation and migration of GBP2-overexpressed HCC cells decreased significantly after STAT1 knockdown(P＜0.05),accompanied by an increase in apoptosis rate(P＜0.001).Conclusion GBP2 downregulation can inhibit the proliferation,migration,and tumorigenicity of HCC cells,and GBP2 knockdown in HCC cells shows a marked enhancement of apoptosis.The expression of GBP2 is positively correlated with that of STAT1 in HCC patients,and STAT1 knockdown can partially alleviate the driving effect of GBP2 overexpression on HCC cells.GBP2 and STAT1 synergistically regulate the development and progression of HCC,which may become a target for HCC treatment.
hepatocellular carcinomaguanylate binding protein 2proliferationmigrationsignal transducer and activator of transcription 1
NETL
NSTL
万方数据
