| BackgroundThe immune system has been reported to play an essential role in the development and progression of cancer.Besides,numerous experiments have validated the hypothesis that this type of competitive endogenous RNA(ceRNA)regulatory mechanism can be involved in immune regulation to affect hepatocellular carcinoma(HCC)tumorigenesis and development.However,the ceRNA network in HCC from the viewpoint of immune regulation is lacking.Our study aimed to construct an immune-related ceRNA network and develop an immune-related lncRNA signature to assess the prognosis of HCC patients for optimizing the treatment.MethodsDifferentially expressed lncRNAs(DEIncRNAs),mRNAs(DEmRNAs)and miRNAs(DEmiRNAs)between the hepatic tumor and the normal tissue in the Cancer Genome Atlas(TCGA)were firstly identified and a ceRNA regulatory network for HCC was constructed after exploring targeting regulatory relations among these differentially expressed RNA.Then we screened out the immune-related lncRNAs,mRNAs and miRNAs in the ceRNA network and an immune-related ceRNA regulatory network was constructed.Based on this,univariate Cox regression and least absolute shrinkage and selection operator(LASSO)Cox regression were successively performed to identify the immune-related prognostic lncRNAs and an immune-related lncRNA prognostic signature was established.Furthermore,survival analysis,gene set enrichment analysis(GSEA)and the correlation analysis of the lncRNA signature with immune cell infiltration and immune check blockade(ICB)therapy-related genes were carried out to confirm its predictive power and biofunctional characteristics.Finally,the bioinformatics analysis,in vitro and in vivo studies were performed to investigate the potential therapeutic target in this signature.ResultsThere were 374 HCC tumor specimens and 50 adjacent normal tissue downloaded from TCGA database and a ceRNA regulatory network for HCC was constructed by DElncRNAs,DEmRNAs and DEmiRNAs.After analyzing the correlation between these DERNAs in the ceRNA network and immune-related genes,an immune-related ceRNA regulatory network for HCC was established by 59 DElncRNAs,21 DEmiRNAs and 26 DEmRNAs.Then,there were 11 prognostic lncRNAs screened out from the immune-related lncRNA in the ceRNA network and a 11-lncRNA prognostic risk model with great predictive power and stability in predicting the overall survival(OS)of HCC patients was established,including C10orf91,SERHL,LINC00491,etc,which might also be considered as an independent prognostic indicator of OS.Moreover,the risk model had high correlation relations with immunologic signatures,immune infiltration and 11 immune checkpoint blockade(ICB)therapy-related genes,such as PD-1,TIM-3,CTLA-4,etc.LINC00491 in the risk model was regarded as a novel potential therapeutic target for HCC.It showed great OS predictive power and might be considered as an independent prognostic indicator of OS.Furthermore,in vitro and in vivo evidence demonstrated that silencing of LINC00491 significantly inhibited proliferation,invasiveness and migration capabilities of HCC cells.ConclusionAn immune-related ceRNA specific regulatory network for HCC was constructed in our study,which might facilitate understanding tumor-immune interaction with great promise for the therapeutic interventions of HCC.Meanwhile,a novel immune-related 11-lncRNA prognostic risk model was established with great predictive power in predicting the OS of HCC patients and high correlation relations with immunologic signatures,immune infiltration and ICB therapy-related genes,which might provide the theoretical support for the application of immune therapy in HCC.LINC00491 in the risk model,which not only could act as an independent prognostic indicator of OS,but also highly correlated with proliferation,invasiveness,and migration capabilities of HCC cells,might be considered as the potential therapeutic target for HCC. |
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