Objectives:Deubiquitinase OTUB2 plays a critical role in the progression of various tumors.However,its specific role in triple-negative breast cancer(TNBC)remains unclear.This study aims to elucidate the biological fu...Objectives:Deubiquitinase OTUB2 plays a critical role in the progression of various tumors.However,its specific role in triple-negative breast cancer(TNBC)remains unclear.This study aims to elucidate the biological function of OTUB2 in TNBC and uncover the underlying mechanisms.Methods:First,we found that the expression of OTUB2 was upregulated in TNBC by bioinformatics analysis,we then validated its expression in TNBC tissues and cells using immunohistochemistry(IHC)and qPCR and plotted the survival curves by Kaplan-Meier method.Gene set enrichment analysis(GSEA)suggested that OTUB2 may be involved in tumor proliferation and metastasis.Further functional assays,including Cell Counting Kit-8(CCK-8),colony formation,Transwell,and wound healing assays,were performed to assess the effects of OTUB2 overexpression and knockdown on TNBC cell proliferation and migration.Additionally,UbiBrowser 2.0 was used to identify OTUB2 substrate proteins and western blotting was conducted to clarify the molecular mechanisms involved.Results:Our results demonstrated that OTUB2 expression was elevated in TNBC and associated with poor prognosis.Overexpression of OTUB2 enhanced the proliferation and migration of TNBC cells,while its knockdown inhibited these processes.Moreover,OTUB2 stabilized tumor necrosis factor receptor-associated factor 6(TRAF6)by deubiquitinating it,leading to activation of the protein kinase B(AKT)pathway.Conclusions:OTUB2 exerts its promoting effects on the progression of TNBC by activating the TRAF6/AKT pathway.展开更多
Gut microbiota is crucial for protecting the homeostasis of immune locally and systemically,and its dysbiosis is essentially correlated to tumorigenesis,cancer progression,and refractoriness to cancer treatments,inclu...Gut microbiota is crucial for protecting the homeostasis of immune locally and systemically,and its dysbiosis is essentially correlated to tumorigenesis,cancer progression,and refractoriness to cancer treatments,including the novel immunotherapy.Increasing evidence unravel the intricate role of gut microbiota in reshaping tumor microenvironment and affecting the efficacy and toxicities of immunotherapy,which shed more light on the future applications of gut microbiota in efficacious biomarker and combination treatment of immunotherapy.To better grasp the underlying crosstalk between gut microbiota and immunotherapy,more experimental and clinical trials are indispensable for the customized gut microbiotabased treatments in cancer patients undergoing immunotherapy.展开更多
Lactate is the end product of glycolysis,and extensive research has shown that lactate participates in various pathophysiological processes.Along with associated hydrogen ions,lactate typically functions as an immunos...Lactate is the end product of glycolysis,and extensive research has shown that lactate participates in various pathophysiological processes.Along with associated hydrogen ions,lactate typically functions as an immunosuppressive negative factor and plays a crucial role in tumor metabolic reprogramming.The recently discovered lactylation is a novel epigenetic modification that,similar to other epigenetic modifications,modifies histones to alter chromatin spatial configuration,thereby affecting DNA accessibility and regulating gene expression.More importantly,the degree of lactylation is closely related to local lactate concentrations,establishing a link between epigenetics and metabolic reprogramming.During cellular metabolism,lactate accumulation promotes histone lysine lactylation in cancer cells and immune cells such as macrophages and T cells,playing an essential role in tumor immune evasion and resistance to immunotherapy.This paper details the role of lactylation modifications in cancer immune evasion and resistance to immunotherapy,providing novel therapeutic directions and targets for cancer treatment.展开更多
基金supported by the National Natural Science Foundation of China(No.82373380,Xinhua Xie).
文摘Objectives:Deubiquitinase OTUB2 plays a critical role in the progression of various tumors.However,its specific role in triple-negative breast cancer(TNBC)remains unclear.This study aims to elucidate the biological function of OTUB2 in TNBC and uncover the underlying mechanisms.Methods:First,we found that the expression of OTUB2 was upregulated in TNBC by bioinformatics analysis,we then validated its expression in TNBC tissues and cells using immunohistochemistry(IHC)and qPCR and plotted the survival curves by Kaplan-Meier method.Gene set enrichment analysis(GSEA)suggested that OTUB2 may be involved in tumor proliferation and metastasis.Further functional assays,including Cell Counting Kit-8(CCK-8),colony formation,Transwell,and wound healing assays,were performed to assess the effects of OTUB2 overexpression and knockdown on TNBC cell proliferation and migration.Additionally,UbiBrowser 2.0 was used to identify OTUB2 substrate proteins and western blotting was conducted to clarify the molecular mechanisms involved.Results:Our results demonstrated that OTUB2 expression was elevated in TNBC and associated with poor prognosis.Overexpression of OTUB2 enhanced the proliferation and migration of TNBC cells,while its knockdown inhibited these processes.Moreover,OTUB2 stabilized tumor necrosis factor receptor-associated factor 6(TRAF6)by deubiquitinating it,leading to activation of the protein kinase B(AKT)pathway.Conclusions:OTUB2 exerts its promoting effects on the progression of TNBC by activating the TRAF6/AKT pathway.
文摘Gut microbiota is crucial for protecting the homeostasis of immune locally and systemically,and its dysbiosis is essentially correlated to tumorigenesis,cancer progression,and refractoriness to cancer treatments,including the novel immunotherapy.Increasing evidence unravel the intricate role of gut microbiota in reshaping tumor microenvironment and affecting the efficacy and toxicities of immunotherapy,which shed more light on the future applications of gut microbiota in efficacious biomarker and combination treatment of immunotherapy.To better grasp the underlying crosstalk between gut microbiota and immunotherapy,more experimental and clinical trials are indispensable for the customized gut microbiotabased treatments in cancer patients undergoing immunotherapy.
文摘Lactate is the end product of glycolysis,and extensive research has shown that lactate participates in various pathophysiological processes.Along with associated hydrogen ions,lactate typically functions as an immunosuppressive negative factor and plays a crucial role in tumor metabolic reprogramming.The recently discovered lactylation is a novel epigenetic modification that,similar to other epigenetic modifications,modifies histones to alter chromatin spatial configuration,thereby affecting DNA accessibility and regulating gene expression.More importantly,the degree of lactylation is closely related to local lactate concentrations,establishing a link between epigenetics and metabolic reprogramming.During cellular metabolism,lactate accumulation promotes histone lysine lactylation in cancer cells and immune cells such as macrophages and T cells,playing an essential role in tumor immune evasion and resistance to immunotherapy.This paper details the role of lactylation modifications in cancer immune evasion and resistance to immunotherapy,providing novel therapeutic directions and targets for cancer treatment.
