Background and Aims:Numerous studies have explored the important role of N6-methyladenosine(m^(6)A)in cancer.Nonetheless,the interaction between m^(6)A and long noncoding RNAs(lncRNAs)is poorly investigated.Herein,we ...Background and Aims:Numerous studies have explored the important role of N6-methyladenosine(m^(6)A)in cancer.Nonetheless,the interaction between m^(6)A and long noncoding RNAs(lncRNAs)is poorly investigated.Herein,we systematically analyzed the role and prognostic value of m^(6)A-related lncRNAs in hepatocellular carcinoma(HCC).Methods:The m^(6)A-related lncRNAs were identified based on the correlation coefficients with m^(6)A-related genes in HCC from The Cancer Genome Atlas.Subsequently,a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses.Univariate and multivariate Cox analyses were used to identify independent prog-nostic factors for overall survival(OS)of HCC;thereafter,a prognostic nomogram was constructed.Results:A total of 259 lncRNAs showed significant correlations with m^(6)A in HCC,while 29 lncRNAs had prognostic significance.Further,six critical m^(6)A-related lncRNAs(NRAV,SNHG3,KDM4A-AS1,AC074117.1,AC025176.1,and AL031985.3)were screened out to construct a novel risk score model which classified HCC patients into high-and low-risk groups.Survival analy-ses revealed that patients in the high-risk group exhibited worse OS,both in the training and validation groups.The risk score was also identified as an independent prognostic factor of OS,and a nomogram was established and verified with superior prediction capacity.Besides,the risk score signifi-cantly correlated with the expression of immune checkpoint genes and immune subtypes.Conclusions:These findings indicated the significant role of m^(6)A-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction.展开更多
Background and Aims:TMCO3,a member of the monovalent cation:proton antiporter-2 family,has been annotated as a Na^(+)/H^(+)antiporter,but its pathophysiological role is still unclear.We aimed to investigate the expres...Background and Aims:TMCO3,a member of the monovalent cation:proton antiporter-2 family,has been annotated as a Na^(+)/H^(+)antiporter,but its pathophysiological role is still unclear.We aimed to investigate the expression profile,prognostic significance,and oncogenic role of TMCO3 in hepatocellular carcinoma(HCC).Methods:Bioinformatic analyses were conducted using transcriptome data from public databases to determine the expression,prognosis,and functional enrichment of TMCO3 in HCC.TMCO3 expression was further validated in an independent HCC cohort from our institution.The oncogenic role of TMCO3 in HCC was evaluated using in vitro and in vivo experiments.Results:The upregulated expression of TMCO3 was identified and verified in multiple HCC cohorts,and worse overall survival and recurrence-free survival were observed in patients with high TMCO3 expression.The overexpression and knockdown of TMCO3 could affect the proliferation and metastasis of HCC cells,which might be associated with the p53-induced cell cycle regulation and epithelial-mesenchymal transition,respectively.Notably,significant correlations were found between dysregulated TMCO3 and various antitumor agents.Its role in sorafenib sensitivity was further identified by in vitro experiments and the potential mechanism might be related to the regulation of apoptosis.Positive correlations were also identified between upregulation of TMCO3 and the increased infiltration of various immune cells and the elevated expression of multiple immune checkpoint genes in HCC.Conclusions:Upregulated TMCO3 could act as an oncogenic mediator and promote sorafenib resistance in HCC,providing a potential therapeutic target for HCC treatment.展开更多
基金supported in part by grants from the GuangdongGuang-dong Natural Science Foundation(Nos.2015A030313038,2015A030312013)Science and Technology Program of Guangzhou City(No.201607010024)Guangdong Key Laboratory of Liver Disease Research(No.2017B030314027).
文摘Background and Aims:Numerous studies have explored the important role of N6-methyladenosine(m^(6)A)in cancer.Nonetheless,the interaction between m^(6)A and long noncoding RNAs(lncRNAs)is poorly investigated.Herein,we systematically analyzed the role and prognostic value of m^(6)A-related lncRNAs in hepatocellular carcinoma(HCC).Methods:The m^(6)A-related lncRNAs were identified based on the correlation coefficients with m^(6)A-related genes in HCC from The Cancer Genome Atlas.Subsequently,a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses.Univariate and multivariate Cox analyses were used to identify independent prog-nostic factors for overall survival(OS)of HCC;thereafter,a prognostic nomogram was constructed.Results:A total of 259 lncRNAs showed significant correlations with m^(6)A in HCC,while 29 lncRNAs had prognostic significance.Further,six critical m^(6)A-related lncRNAs(NRAV,SNHG3,KDM4A-AS1,AC074117.1,AC025176.1,and AL031985.3)were screened out to construct a novel risk score model which classified HCC patients into high-and low-risk groups.Survival analy-ses revealed that patients in the high-risk group exhibited worse OS,both in the training and validation groups.The risk score was also identified as an independent prognostic factor of OS,and a nomogram was established and verified with superior prediction capacity.Besides,the risk score signifi-cantly correlated with the expression of immune checkpoint genes and immune subtypes.Conclusions:These findings indicated the significant role of m^(6)A-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction.
基金supported in part by grants from the Guangdong Natural Science Foundation(Nos.2015A030313038 and 2015A030312013)Guangdong Key Laboratory of Liver Disease Research(No.2017B030314027)National Natural Science Foundation of China(Nos.81770648 and 81972286).
文摘Background and Aims:TMCO3,a member of the monovalent cation:proton antiporter-2 family,has been annotated as a Na^(+)/H^(+)antiporter,but its pathophysiological role is still unclear.We aimed to investigate the expression profile,prognostic significance,and oncogenic role of TMCO3 in hepatocellular carcinoma(HCC).Methods:Bioinformatic analyses were conducted using transcriptome data from public databases to determine the expression,prognosis,and functional enrichment of TMCO3 in HCC.TMCO3 expression was further validated in an independent HCC cohort from our institution.The oncogenic role of TMCO3 in HCC was evaluated using in vitro and in vivo experiments.Results:The upregulated expression of TMCO3 was identified and verified in multiple HCC cohorts,and worse overall survival and recurrence-free survival were observed in patients with high TMCO3 expression.The overexpression and knockdown of TMCO3 could affect the proliferation and metastasis of HCC cells,which might be associated with the p53-induced cell cycle regulation and epithelial-mesenchymal transition,respectively.Notably,significant correlations were found between dysregulated TMCO3 and various antitumor agents.Its role in sorafenib sensitivity was further identified by in vitro experiments and the potential mechanism might be related to the regulation of apoptosis.Positive correlations were also identified between upregulation of TMCO3 and the increased infiltration of various immune cells and the elevated expression of multiple immune checkpoint genes in HCC.Conclusions:Upregulated TMCO3 could act as an oncogenic mediator and promote sorafenib resistance in HCC,providing a potential therapeutic target for HCC treatment.
