Background and Aims:The growing knowledge of ferroptosis has suggested the regulatory role of ferroptosis in hepatocellular carcinoma(HCC),but the pertinent molecular mechanisms remain unclear.Herein,this study invest...Background and Aims:The growing knowledge of ferroptosis has suggested the regulatory role of ferroptosis in hepatocellular carcinoma(HCC),but the pertinent molecular mechanisms remain unclear.Herein,this study investigated the mechanistic basis of ferroptosis-related genes(ferrGenes)in the growth of HCC.Methods:Differentially expressed human ferrGenes and tumor-related transcription factors(TFs)were obtained from the The Cancer Genome Atlas(TCGA)dataset and the GTEx dataset.Spearman method-based correlation analysis were conducted to construct TF-ferrGene coexpression regulatory network.Key genes associated with prognosis were singled out with Lasso regression and multivariate Cox analysis to construct the prognostic risk model.Then the accuracy and independent prognostic ability of the model were evaluated.Expression of CENPA and STMN1 was determined in clinical HCC tissues and HCC cells,and their binding was analyzed with dual-luciferase and chromatin immunoprecipitation(ChIP)assays.Furthermore,ectopic expression and knockdown assays were performed in HCC cells to assess the effect of CENPA and STMN1 on ferroptosis and malignant phenotypes.Results:The prognostic risk model constructed based on the eight TF-ferrGene regulatory network-related genes accurately predicted the prognosis of HCC patients.It was strongly related to the clinical characteristics of HCC patients.Moreover,CENPA/STMN1 might be a key TF-ferrGene regulatory network in ferroptosis of HCC.CENPA and STMN1 were overexpressed in HCC tissues and cells.Additionally,CENPA facilitated STMN1 transcription by binding to STMN1 promoter,thus facilitating the malignant phenotypes and suppressing the ferroptosis of HCC cells.Conclusions:Taken together,CENPA curbs the ferroptosis of HCC cells by upregulating STMN1 transcription,thereby promoting HCC growth.展开更多
基金supported by Hunan Provincial Natural Science Foundation(2019JJ50321)Hunan Provincial Graduate Scientific Research Innovation Project(QL20220133).
文摘Background and Aims:The growing knowledge of ferroptosis has suggested the regulatory role of ferroptosis in hepatocellular carcinoma(HCC),but the pertinent molecular mechanisms remain unclear.Herein,this study investigated the mechanistic basis of ferroptosis-related genes(ferrGenes)in the growth of HCC.Methods:Differentially expressed human ferrGenes and tumor-related transcription factors(TFs)were obtained from the The Cancer Genome Atlas(TCGA)dataset and the GTEx dataset.Spearman method-based correlation analysis were conducted to construct TF-ferrGene coexpression regulatory network.Key genes associated with prognosis were singled out with Lasso regression and multivariate Cox analysis to construct the prognostic risk model.Then the accuracy and independent prognostic ability of the model were evaluated.Expression of CENPA and STMN1 was determined in clinical HCC tissues and HCC cells,and their binding was analyzed with dual-luciferase and chromatin immunoprecipitation(ChIP)assays.Furthermore,ectopic expression and knockdown assays were performed in HCC cells to assess the effect of CENPA and STMN1 on ferroptosis and malignant phenotypes.Results:The prognostic risk model constructed based on the eight TF-ferrGene regulatory network-related genes accurately predicted the prognosis of HCC patients.It was strongly related to the clinical characteristics of HCC patients.Moreover,CENPA/STMN1 might be a key TF-ferrGene regulatory network in ferroptosis of HCC.CENPA and STMN1 were overexpressed in HCC tissues and cells.Additionally,CENPA facilitated STMN1 transcription by binding to STMN1 promoter,thus facilitating the malignant phenotypes and suppressing the ferroptosis of HCC cells.Conclusions:Taken together,CENPA curbs the ferroptosis of HCC cells by upregulating STMN1 transcription,thereby promoting HCC growth.
