The dysregulation of transcription factors is widely associated with tumorigenesis.As the most well-defined transcription factor in multiple types of cancer,c-Myc can transform cells by transactivating various downstr...The dysregulation of transcription factors is widely associated with tumorigenesis.As the most well-defined transcription factor in multiple types of cancer,c-Myc can transform cells by transactivating various downstream genes.Given that there is no effective way to directly inhibit c-Myc,c-Myc targeting strategies hold great potential for cancer therapy.In this study,we found that WSB1,which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples,is a direct target gene of c-Myc,and can positively regulate c-Myc expression,which forms a feedforward circuit promoting cancer development.RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted cMyc expression through theβ-catenin pathway.Mechanistically,WSB1 affectedβ-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptorβ-TRCP recruitment,which inhibited the ubiquitination ofβ-catenin and transactivated c-Myc.Of interest,the effect of WSB1 on c-Myc was independent of its E3 ligase activity.Moreover,overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression.Thus,our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role,highlighting a potential c-Myc intervention strategy in cancer treatment.展开更多
Objective:A strong association exists between metabolic syndrome and psoriasis.The current study was performed to explore the gene regulation of metabolic syndrome in patients with psoriasis.Methods:Patients were asse...Objective:A strong association exists between metabolic syndrome and psoriasis.The current study was performed to explore the gene regulation of metabolic syndrome in patients with psoriasis.Methods:Patients were assessed for psoriasis and metabolic syndrome clinically (Psoriasis Area and Severity Index,height,weight,waist circumference,and blood pressure) and biochemically (lipid profile and fasting blood sugar concentration).Systemic gene regulation was first explored by microarray and analyzed using Transcriptome Analysis Console Software,after which two selected upregulated genes were further validated using polymerase chain reaction and enzyme-linked immunosorbent assay and analyzed using independent samplet test.Results:The analysis showed 7,269 upregulated and 3 downregulated genes at a fold change of 2 andP value of < 0.05;only 17 genes were upregulated and none were downregulated at a fold change of 8 andP value of < 0.005.Comparison with 22 previously reported potential biomarkers of metabolic syndrome in patients with psoriasis showed that the levels of 16 biomarkers aligned with the gene regulation observed in the current study.In particular,theREL transcript was upregulated 12-fold (P = 8.16 × 10-17),while theWSB1 transcript was upregulated 9-fold (P = 9.87 × 10-13).Validation showed thatREL was also upregulated 2-fold in the polymerase chain reaction,and its protein was expressed at 7.140 ng/mLvs.undetectable levels in the cases (P = 0.048).However,WSB1 was upregulated 2-fold in the polymerase chain reaction compared with controls,and unexpectedly,its protein was undetectable in cases but detectable in controls (P = 0.018).Conclusion:The upregulation ofREL andWSB1 was observed in patients with psoriasis and metabolic syndrome,the clinical application ofREL andWSB1 as biomarkers needs further validation for potential future implications in clinical practice.展开更多
基金supported by grants from Zhejiang Provincial Natural Science Foundation(No.Y18H310001 to Ji Cao,China)the National Natural Science Foundation of China(No.81872885 to Ji Cao+1 种基金No.81625024 to Bo Yang)the Talent Project of Zhejiang Association for Science and Technology(No.2018YCGC002 to Ji Cao,China)。
文摘The dysregulation of transcription factors is widely associated with tumorigenesis.As the most well-defined transcription factor in multiple types of cancer,c-Myc can transform cells by transactivating various downstream genes.Given that there is no effective way to directly inhibit c-Myc,c-Myc targeting strategies hold great potential for cancer therapy.In this study,we found that WSB1,which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples,is a direct target gene of c-Myc,and can positively regulate c-Myc expression,which forms a feedforward circuit promoting cancer development.RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted cMyc expression through theβ-catenin pathway.Mechanistically,WSB1 affectedβ-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptorβ-TRCP recruitment,which inhibited the ubiquitination ofβ-catenin and transactivated c-Myc.Of interest,the effect of WSB1 on c-Myc was independent of its E3 ligase activity.Moreover,overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression.Thus,our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role,highlighting a potential c-Myc intervention strategy in cancer treatment.
基金supported by Arabian Gulf University, Bahrain(No. E005-PI-04/17)。
文摘Objective:A strong association exists between metabolic syndrome and psoriasis.The current study was performed to explore the gene regulation of metabolic syndrome in patients with psoriasis.Methods:Patients were assessed for psoriasis and metabolic syndrome clinically (Psoriasis Area and Severity Index,height,weight,waist circumference,and blood pressure) and biochemically (lipid profile and fasting blood sugar concentration).Systemic gene regulation was first explored by microarray and analyzed using Transcriptome Analysis Console Software,after which two selected upregulated genes were further validated using polymerase chain reaction and enzyme-linked immunosorbent assay and analyzed using independent samplet test.Results:The analysis showed 7,269 upregulated and 3 downregulated genes at a fold change of 2 andP value of < 0.05;only 17 genes were upregulated and none were downregulated at a fold change of 8 andP value of < 0.005.Comparison with 22 previously reported potential biomarkers of metabolic syndrome in patients with psoriasis showed that the levels of 16 biomarkers aligned with the gene regulation observed in the current study.In particular,theREL transcript was upregulated 12-fold (P = 8.16 × 10-17),while theWSB1 transcript was upregulated 9-fold (P = 9.87 × 10-13).Validation showed thatREL was also upregulated 2-fold in the polymerase chain reaction,and its protein was expressed at 7.140 ng/mLvs.undetectable levels in the cases (P = 0.048).However,WSB1 was upregulated 2-fold in the polymerase chain reaction compared with controls,and unexpectedly,its protein was undetectable in cases but detectable in controls (P = 0.018).Conclusion:The upregulation ofREL andWSB1 was observed in patients with psoriasis and metabolic syndrome,the clinical application ofREL andWSB1 as biomarkers needs further validation for potential future implications in clinical practice.
