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Expression,Significant And Function Of ASF1B In Hepatocellular Carcinoma

Posted on:2022-10-25Degree:MasterType:Thesis
Country:ChinaCandidate:Z K XiaoFull Text:PDF
GTID:2504306335991599Subject:Surgery (general surgery)
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Objective Anti-silencing function 1B(ASFIB)is a histone H3/H4 chaperone involved in DNA replication and repair as well as transcriptional regulation,ASF1B regulates the function of chromatin and has been proved to contribute to tumorigenesis.Previous studies have shown that ASF IB gene is closely related to the development and progression of cervical cancer,lung cancer,clear cell renal cell carcinoma and other tumors.However,the role of ASF 1B gene in hepatocellular carcinoma(HCC)remains unclear.In this study,to explore the expression level of ASF 1B gene in HCC,the relationship between ASF 1B gene expression level and HCC clinicopathological characteristics,and its effect of expression level on prognosis.To explore the effect of overexpression of ASF1B on the biological functions of HCC cell lines.Bioinformatics analysis was used to predict its potential biological function in HCC.Methods Immunohistochemistry and Western blotting(WB)was used to detected the expression level of ASF1B in HCC.Clinical and transcription data of HCC patients were collected from TCGA database to analyze the difference of the expression level of ASF 1B in HCC tissues and normal liver tissues at the mRNA level.The relationship between ASF1B expression level and the clinicopathological characteristics as well as prognosis of HCC patients were analyzed.Effects of overexpression of ASF1B on proliferation,metastasis,invasion and apoptosis of HepG2 cells was explored.Gene set enrichment analysis was performed.Results Compared with normal liver tissues,the expression levels of ASF1B gene in HCC tissues were higher at mRNA level(P=0.002)and protein level(P=0.000).high expression of ASF1B in HCC was correlated with high tumor extent(P=0.016),poor differentiated(P=0.000),advanced stage(P=0.013)and high level of alpha-fetoprotein(P=0.000).Patients with high expression of ASF 1B had worse prognosis(P=0.030).Multivariate Cox regression analysis showed that ASF IB was an independent risk factor for HOC patients(P=0.008).Overexpression of ASF1B not only promoted the ability of proliferation,migration and invasion in HepG2 cells but also inhibited cells apoptosis.GSEA showed the enrichment of DNA repair,nucleotide excision repair,cell cycle checkpoint,signaling by notch4,G1to S cell cycle control,TNFR1 pathway,E2F pathway and E2F pathway in ASF1B high-expression phenotype.Conclusion The expression level of ASF 1B in HCC is high,which is related to many malignant phenotypes.Patients with high expression of ASF1B have worse prognosis,and the expression level of ASF1B was an independent risk factor for prognosis of HCC patients.Overexpression of ASF1B can promote the proliferation,metastasis and invasion ability of HepG2 cells and inhibit their apoptosis in vitro.In conclusion,ASF 1B has the potential to become a new prognostic indicator and therapeutic target of HCC.
Keywords/Search Tags:ASF1B, HCC, Expression, Prognosis, Overexpression
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