Transcription factor forkhead box P3(Foxp3)+regulatory T(Treg)cells are receiving increasing attention because this unique subset of T cells is characterized by exerting negative regulatory function of cellular immune...Transcription factor forkhead box P3(Foxp3)+regulatory T(Treg)cells are receiving increasing attention because this unique subset of T cells is characterized by exerting negative regulatory function of cellular immune responses.The resultant suppression of anti-tumor immunity in the tumor microenvironment(TME)is regarded as a major obstacle to immunotherapies in a plethora of cancers.Thus,an integrated understanding of the intrinsic correlation between tumors and Treg cell biology is urgently required.This review focuses on the peculiar biochemical effects of tumor metabolic environments on Tregs and how Tregs orchestrate internal metabolic switches and altered metabolic pathways and molecules to survive and function after the remodeling of homeostasis and specialization,providing new directions for immunotherapies.展开更多
Background:Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer(PCa),the long tail of cancer genes remains to be defined.Goosecoid(GSC)has been implicated ...Background:Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer(PCa),the long tail of cancer genes remains to be defined.Goosecoid(GSC)has been implicated in cancer development.However,the comprehensive biological role of GSC in pan-cancer,specifically in PCa,remains unexplored.The aim of this study was to investigate the role of GSC in PCa development.Methods:We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Omnibus,German Cancer Research Center,and our in-house cohorts.First,we evaluated the expression of GSC and its association with patient prognosis,and identified GSC-relevant genetic alterations in cancers.Further,we focused on the clinical characterization and prognostic analysis of GSC in PCa.To understand the transcriptional regulation of GSC by E2F transcription factor 1(E2F1),we performed chromatin immunoprecipitation quantitative polymerase chain reaction(qPCR).Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib.Results:GSC expression was elevated in various tumors and significantly correlated with patient prognosis.The alterations of GSC contribute to the progression of various tumors especially in PCa.Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes.Further,GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score,advanced tumor stage,lymph node metastasis,and elevated prostate-specific antigen(PSA)levels.Mechanistically,the transcription factor,E2F1,stimulates GSC by binding to its promoter region.Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment.Conclusions:GSC was highly overexpressed and strongly correlated with patient prognosis in PCa.We found that GSC,regulated by E2F1,acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.展开更多
文摘Transcription factor forkhead box P3(Foxp3)+regulatory T(Treg)cells are receiving increasing attention because this unique subset of T cells is characterized by exerting negative regulatory function of cellular immune responses.The resultant suppression of anti-tumor immunity in the tumor microenvironment(TME)is regarded as a major obstacle to immunotherapies in a plethora of cancers.Thus,an integrated understanding of the intrinsic correlation between tumors and Treg cell biology is urgently required.This review focuses on the peculiar biochemical effects of tumor metabolic environments on Tregs and how Tregs orchestrate internal metabolic switches and altered metabolic pathways and molecules to survive and function after the remodeling of homeostasis and specialization,providing new directions for immunotherapies.
基金supported by the National Natural Science Foundation of China(Nos.82173068,81974400)the Applied Basic Research Plan from Qinghai Provincial Department of Science and Technology(No.2021-ZJ-723).
文摘Background:Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer(PCa),the long tail of cancer genes remains to be defined.Goosecoid(GSC)has been implicated in cancer development.However,the comprehensive biological role of GSC in pan-cancer,specifically in PCa,remains unexplored.The aim of this study was to investigate the role of GSC in PCa development.Methods:We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Omnibus,German Cancer Research Center,and our in-house cohorts.First,we evaluated the expression of GSC and its association with patient prognosis,and identified GSC-relevant genetic alterations in cancers.Further,we focused on the clinical characterization and prognostic analysis of GSC in PCa.To understand the transcriptional regulation of GSC by E2F transcription factor 1(E2F1),we performed chromatin immunoprecipitation quantitative polymerase chain reaction(qPCR).Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib.Results:GSC expression was elevated in various tumors and significantly correlated with patient prognosis.The alterations of GSC contribute to the progression of various tumors especially in PCa.Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes.Further,GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score,advanced tumor stage,lymph node metastasis,and elevated prostate-specific antigen(PSA)levels.Mechanistically,the transcription factor,E2F1,stimulates GSC by binding to its promoter region.Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment.Conclusions:GSC was highly overexpressed and strongly correlated with patient prognosis in PCa.We found that GSC,regulated by E2F1,acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.
