Objectives:Triple-negative breast cancer(TNBC)is the breast cancer subtype with the poorest prognosis.This study aimed to elucidate the molecular pathways through which isoliquiritigenin(ISL),a natural chalcone compou...Objectives:Triple-negative breast cancer(TNBC)is the breast cancer subtype with the poorest prognosis.This study aimed to elucidate the molecular pathways through which isoliquiritigenin(ISL),a natural chalcone compound derived fromlicorice and other plant roots,targets interferon regulatory factor 5(IRF5)in TNBC.Methods:TNBC cell lines were cultured and subjected to IRF5 knockdown using short hairpin RNA.Cell proliferation was assessed by cell counting kit-8(CCK-8)assay and colony formation assays.Western blotting and quantitative reverse transcription polymerase chain reaction(RT-PCR)were employed to measure expression levels of IRF5,solute carrier family 7 member 5(SLC7A5),and indoleamine 2,3-dioxygenase 1(IDO1).Intracellular tryptophan and its metabolites were quantified using commercially available assay kits and high-performance liquid chromatography(HPLC).TNBC cells were treated with various concentrations of ISL to evaluate its effects on proliferation and tryptophanmetabolism.Results:IRF5 was highly expressed in TNBC cell lines.Silencing IRF5 significantly inhibited cellular proliferation and growth.Knockdown of IRF5 reduced the expression of SLC7A5 and IDO1,leading to decreased intracellular levels of tryptophan and its metabolites.ISL markedly suppressed TNBC cell proliferation and disrupted tryptophan metabolism in tumor cells.Conclusion:ISL may inhibit TNBC progression by downregulating IRF5 and interfering with SLC7A5/IDO1-mediated tryptophan metabolic reprogramming,suggesting a potential therapeutic mechanism for TNBC treatment.展开更多
AIM To investigate possible effects of IRF5 polymorphisms in the 3'UTR region of the IFR5 locus on susceptibilityto hepatitis B virus(HBV)infection and progression of liver diseases among clinically classified Vie...AIM To investigate possible effects of IRF5 polymorphisms in the 3'UTR region of the IFR5 locus on susceptibilityto hepatitis B virus(HBV)infection and progression of liver diseases among clinically classified Vietnamese patients.METHODS Four IFR5 SNPs(rs13242262 A/T,rs77416878 C/T,rs10488630 A/G,and rs2280714 T/C)were genotyped in clinically classified HBV patients[chronic hepatitis B(CHB).n=99;liver cirrhosis(LC),n=131;hepatocellular carcinoma(HCC),n=149]and in 242 healthy controls by direct sequencing and Taq Man realtime PCR assays.RESULTS Comparing patients and controls,no significant association was observed for the four IFR5 variants.However,the alleles rs13242262 T and rs10488630 G contributed to an increased risk of liver cirrhosis(LC vs CHB:OR=1.5,95%CI:1.1-2.3,adjusted P=0.04;LC vs CHB:OR=1.7,95%CI:1.1-2.6,adjusted P=0.019).Haplotype IRF5*TCGT constructed from 4 SNPs was observed frequently in LC compared to CHB patients(OR=2.1,95%CI:1.2-3.3,adjusted P=0.008).Haplotype IRF5*TCAT occurred rather among CHB patients than in the other HBV patient groups(LC vs CHB:OR=0.4,95%CI:0.2-0.8,adjusted P=0.03;HCC vs CHB:OR=0.3,95%CI:0.15-0.7,adjusted P=0.003).The IRF5*TCAT haplotype was also associated with increased levels of ALT,AST and bilirubin.CONCLUSION Our study shows that IFR5 variants may contribute as a host factor in determining the pathogenesis in chronic HBV infections.展开更多
基金supported by the Science and Technology Program of Guangzhou(No.202103000020).
文摘Objectives:Triple-negative breast cancer(TNBC)is the breast cancer subtype with the poorest prognosis.This study aimed to elucidate the molecular pathways through which isoliquiritigenin(ISL),a natural chalcone compound derived fromlicorice and other plant roots,targets interferon regulatory factor 5(IRF5)in TNBC.Methods:TNBC cell lines were cultured and subjected to IRF5 knockdown using short hairpin RNA.Cell proliferation was assessed by cell counting kit-8(CCK-8)assay and colony formation assays.Western blotting and quantitative reverse transcription polymerase chain reaction(RT-PCR)were employed to measure expression levels of IRF5,solute carrier family 7 member 5(SLC7A5),and indoleamine 2,3-dioxygenase 1(IDO1).Intracellular tryptophan and its metabolites were quantified using commercially available assay kits and high-performance liquid chromatography(HPLC).TNBC cells were treated with various concentrations of ISL to evaluate its effects on proliferation and tryptophanmetabolism.Results:IRF5 was highly expressed in TNBC cell lines.Silencing IRF5 significantly inhibited cellular proliferation and growth.Knockdown of IRF5 reduced the expression of SLC7A5 and IDO1,leading to decreased intracellular levels of tryptophan and its metabolites.ISL markedly suppressed TNBC cell proliferation and disrupted tryptophan metabolism in tumor cells.Conclusion:ISL may inhibit TNBC progression by downregulating IRF5 and interfering with SLC7A5/IDO1-mediated tryptophan metabolic reprogramming,suggesting a potential therapeutic mechanism for TNBC treatment.
基金Supported by NAFOSTED,No.108.02-2017.15BMBF,No.01DP17047
文摘AIM To investigate possible effects of IRF5 polymorphisms in the 3'UTR region of the IFR5 locus on susceptibilityto hepatitis B virus(HBV)infection and progression of liver diseases among clinically classified Vietnamese patients.METHODS Four IFR5 SNPs(rs13242262 A/T,rs77416878 C/T,rs10488630 A/G,and rs2280714 T/C)were genotyped in clinically classified HBV patients[chronic hepatitis B(CHB).n=99;liver cirrhosis(LC),n=131;hepatocellular carcinoma(HCC),n=149]and in 242 healthy controls by direct sequencing and Taq Man realtime PCR assays.RESULTS Comparing patients and controls,no significant association was observed for the four IFR5 variants.However,the alleles rs13242262 T and rs10488630 G contributed to an increased risk of liver cirrhosis(LC vs CHB:OR=1.5,95%CI:1.1-2.3,adjusted P=0.04;LC vs CHB:OR=1.7,95%CI:1.1-2.6,adjusted P=0.019).Haplotype IRF5*TCGT constructed from 4 SNPs was observed frequently in LC compared to CHB patients(OR=2.1,95%CI:1.2-3.3,adjusted P=0.008).Haplotype IRF5*TCAT occurred rather among CHB patients than in the other HBV patient groups(LC vs CHB:OR=0.4,95%CI:0.2-0.8,adjusted P=0.03;HCC vs CHB:OR=0.3,95%CI:0.15-0.7,adjusted P=0.003).The IRF5*TCAT haplotype was also associated with increased levels of ALT,AST and bilirubin.CONCLUSION Our study shows that IFR5 variants may contribute as a host factor in determining the pathogenesis in chronic HBV infections.
