Tanshinone IIA,one of the main ingredients of Danshen,is used to treat hepatocellular carcinoma(HCC).However,potential targets of the molecule in the therapy of HCC are unknown.Methods:In this study,we collected the t...Tanshinone IIA,one of the main ingredients of Danshen,is used to treat hepatocellular carcinoma(HCC).However,potential targets of the molecule in the therapy of HCC are unknown.Methods:In this study,we collected the tanshinone IIA targets from public databases for investigation.We screened differentially expressed genes(DEGs)across HCC and normal tissues using mRNA expression profiles from The Cancer Genome Atlas(TCGA).Univariate Cox regression analysis and least absolute shrinkage and selection operator(LASSO)Cox regression models were used to identify and construct the prognostic gene signature.Results:Finally,we discovered common genes across tanshinone IIA targets and HCC DEGs.We reported Fatty acid binding protein-6(FABP6),Polo-like Kinase 1(PLK1),deoxythymidylate kinase(DTYMK),Uridine Cytidine Kinase 2(UCK2),Enhancer of Zeste Homolog 2(EZH2),and Cytochrome P4502C9(CYP2C9)as components of a gene signature.The six-gene signature’s prognostic ability was evaluated using the Kaplan-Meier curve,time-dependent receiver operating characteristic(ROC),multivariate Cox regression analysis,and the nomogram.The mRNA level and protein expression of UCK2 were experimentally validated after treatment with different concentrations of tanshinone IIA in HEPG2 cells.CIBERSORTx,TIMER2.0,and GEPIA2 tools were employed to explore the relationship between the prognostic signature and immune cell infiltration.Conclusion:We established a six-gene signature as a reliable model with significant therapeutic possibility for prognosis and overall survival estimation in HCC patients,which might also benefit medical decision-making for appropriate treatment.展开更多
Dear Editor,Artemisinin,which has potent antimalarial properties,is a sesquiterpene endoperoxide originally isolated from the traditional Chinese medicinal plant Artemisia annua.However,the artemisinin content in wild...Dear Editor,Artemisinin,which has potent antimalarial properties,is a sesquiterpene endoperoxide originally isolated from the traditional Chinese medicinal plant Artemisia annua.However,the artemisinin content in wild-type(WT)A.annua is low(1-10 mg/g dry weight),leading to its erratic supply and price fluctuations[1].展开更多
Artemisia annua,a traditional Chinese medicinal plant,remains the only plant source for artemisinin production,yet few genes have been identified to be involved in both the response to biotic stresses,such as pathogen...Artemisia annua,a traditional Chinese medicinal plant,remains the only plant source for artemisinin production,yet few genes have been identified to be involved in both the response to biotic stresses,such as pathogens,and artemisinin biosynthesis.Here,we isolated and identified the WRKY transcription factor(TF)AaWRKY17,which could significantly increase the artemisinin content and resistance to Pseudomonas syringae in A.annua.Yeast one-hybrid(Y1H),dual-luciferase(dual-LUC),and electrophoretic mobility shift assay(EMSA)results showed that AaWRKY17 directly bound to the W-box motifs in the promoter region of the artemisinin biosynthetic pathway gene amorpha-4,11-diene synthase(ADS)and promoted its expression.Real-time quantitative PCR(RT-qPCR)analysis revealed that the transcript levels of two defense marker genes,Pathogenesis-Related 5(PR5)and NDR1/HIN1-LIKE 10(NHL10),were greatly increased in AaWRKY17-overexpressing transgenic A.annua plants.Additionally,overexpression of AaWRKY17 in A.annua resulted in decreased susceptibility to P.syringae.These results indicated that AaWRKY17 acted as a positive regulator in response to P.syringae infection.Together,our findings demonstrated that the novel WRKY transcription factor AaWRKY17 could potentially be used in transgenic breeding to improve the content of artemisinin and pathogen tolerance in A.annua.展开更多
基金funded by the Sichuan Natural Science Foundation(No.2022NSFSCO654)the Radiation Oncology Key Laboratory of Sichuan Province Open Fund(No.2020FSZLX-03)the UESTC-Sichuan Cancer Hospital 2021 Medical-Engineering Oncology Innovation Fund(No.ZYGX2021YGCX013).
文摘Tanshinone IIA,one of the main ingredients of Danshen,is used to treat hepatocellular carcinoma(HCC).However,potential targets of the molecule in the therapy of HCC are unknown.Methods:In this study,we collected the tanshinone IIA targets from public databases for investigation.We screened differentially expressed genes(DEGs)across HCC and normal tissues using mRNA expression profiles from The Cancer Genome Atlas(TCGA).Univariate Cox regression analysis and least absolute shrinkage and selection operator(LASSO)Cox regression models were used to identify and construct the prognostic gene signature.Results:Finally,we discovered common genes across tanshinone IIA targets and HCC DEGs.We reported Fatty acid binding protein-6(FABP6),Polo-like Kinase 1(PLK1),deoxythymidylate kinase(DTYMK),Uridine Cytidine Kinase 2(UCK2),Enhancer of Zeste Homolog 2(EZH2),and Cytochrome P4502C9(CYP2C9)as components of a gene signature.The six-gene signature’s prognostic ability was evaluated using the Kaplan-Meier curve,time-dependent receiver operating characteristic(ROC),multivariate Cox regression analysis,and the nomogram.The mRNA level and protein expression of UCK2 were experimentally validated after treatment with different concentrations of tanshinone IIA in HEPG2 cells.CIBERSORTx,TIMER2.0,and GEPIA2 tools were employed to explore the relationship between the prognostic signature and immune cell infiltration.Conclusion:We established a six-gene signature as a reliable model with significant therapeutic possibility for prognosis and overall survival estimation in HCC patients,which might also benefit medical decision-making for appropriate treatment.
基金This work was supported by National Key R&D Program of China(2018YFA0900600)the Bill&Melinda Gates Foundation(OPP1199872 and INV-027291)+6 种基金the China Postdoctoral Science Foundation(2022M722851)the National Natural Science Foundation of China(82274047,31770327,32070329,82003889)SJTU Trans-med Awards Research(20190104)SJTU Global Strategic Partnership Fund(2020 SJTU-CORNELL)Zhejiang Provincial Natural Science Foundation of China(LQ21H280004)National Young Qihuang Scholars Training Programthe National‘Ten-thousand Talents Program’for Leading Talents of Science and Technology Innovation in China.
文摘Dear Editor,Artemisinin,which has potent antimalarial properties,is a sesquiterpene endoperoxide originally isolated from the traditional Chinese medicinal plant Artemisia annua.However,the artemisinin content in wild-type(WT)A.annua is low(1-10 mg/g dry weight),leading to its erratic supply and price fluctuations[1].
基金This work was supported by the National Key R&D Program of China(2018YFA0900600)the Bill&Melinda Gates Foundation(OPP1199872 and INV-027291)+1 种基金SJTU Trans-med Awards Research(20190104)the SJTU Global Strategic Partnership Fund(2020 SJTU-CORNELL).
文摘Artemisia annua,a traditional Chinese medicinal plant,remains the only plant source for artemisinin production,yet few genes have been identified to be involved in both the response to biotic stresses,such as pathogens,and artemisinin biosynthesis.Here,we isolated and identified the WRKY transcription factor(TF)AaWRKY17,which could significantly increase the artemisinin content and resistance to Pseudomonas syringae in A.annua.Yeast one-hybrid(Y1H),dual-luciferase(dual-LUC),and electrophoretic mobility shift assay(EMSA)results showed that AaWRKY17 directly bound to the W-box motifs in the promoter region of the artemisinin biosynthetic pathway gene amorpha-4,11-diene synthase(ADS)and promoted its expression.Real-time quantitative PCR(RT-qPCR)analysis revealed that the transcript levels of two defense marker genes,Pathogenesis-Related 5(PR5)and NDR1/HIN1-LIKE 10(NHL10),were greatly increased in AaWRKY17-overexpressing transgenic A.annua plants.Additionally,overexpression of AaWRKY17 in A.annua resulted in decreased susceptibility to P.syringae.These results indicated that AaWRKY17 acted as a positive regulator in response to P.syringae infection.Together,our findings demonstrated that the novel WRKY transcription factor AaWRKY17 could potentially be used in transgenic breeding to improve the content of artemisinin and pathogen tolerance in A.annua.
