Epidemiological studies indicate that prostate cancer(PCa)is the second prevalent malignant tumor affecting men globally.Environmental pollution such as cigarette smoke is one of the important risk factors for the dev...Epidemiological studies indicate that prostate cancer(PCa)is the second prevalent malignant tumor affecting men globally.Environmental pollution such as cigarette smoke is one of the important risk factors for the development of prostate cancer.However,as one of the main carcinogens in cigarette smoke,the role of benzo[a]pyrene(BaP)in prostate cancer is still unclear.The current study aimed to investgate the impacts of BaP exposure on the progression of PCa towardmalignancy and the regulation of the immune microenvironment.We verified that BaP exposure can promote the proliferation,migration,and apoptosis of prostate cancer cells through in vitro experiments.We constructed a subcutaneous xenograft tumor model of BaP exposure mouse and found that can promote the proliferation of tumors in vivo.Organoids-driven by PCa patients showed higher growth rate under BaP exposure.Flow cytometric analysis demonstrated a remarkable decrease in CD4^(+)T and CD8^(+)T cell infiltration levels.Moreover,we identified four genes(Mdm2,Ar,Foxo1,Crebbp)were strongly associated with BaP exposure by combining mouse tumor RNA-seq and CTD database.Additionally,a nomogram integrating clinicopathological features was constructed to assess the prognosis of prostate cancer patients under BaP exposure.This study systematically proved that BaP exposure promotes malignant progression of PCa and suppresses the immune microenvironment,in which Mdm2,Ar,Foxo1,Crebbp may play a crucial role in inhibiting apoptosis.These findings offer novel insights into themechanisms via which BaP exposure contributes to PCa development.展开更多
Interferon regulatory factors(IRFs)are transcription factors with a conserved N-terminal helix-loop-helix DNA-binding domain 1.IRF family plays a pivotal role in regulating interferon transcription,immune cell develop...Interferon regulatory factors(IRFs)are transcription factors with a conserved N-terminal helix-loop-helix DNA-binding domain 1.IRF family plays a pivotal role in regulating interferon transcription,immune cell development,cell growth,apoptosis,and oncogenesis.2 Despite considerable research,the roles of IRFs in cancer development,metastasis,drug resistance,and prognosis remain unclear.Through multidimensional correlation analysis,we examined the association between IRFs and various cancer characteristics,including clinical and immune subtype analysis,stemness,tumor microenvironment(TME),and drug sensitivity,by utilizing The Cancer Genome Atlas(TCGA)data.Moreover,the classification and prognostic role of IRF1 were further validated through immunohistochemistry staining of kidney renal papillary cell carcinoma(KIRP)clinical tissues.This research enriches our understanding of the IRFs’roles in cancer and their clinical applications.展开更多
基金supported by the National Key Research and Development Program of China(No.2022YFB3804504)the National Natural Science Foundation of China,Youth Project(Nos.82101838,82203367,82203505,and 82203403)the Experimental Animal Fund of Shanghai Science and Technology Commission(No.22140903800).
文摘Epidemiological studies indicate that prostate cancer(PCa)is the second prevalent malignant tumor affecting men globally.Environmental pollution such as cigarette smoke is one of the important risk factors for the development of prostate cancer.However,as one of the main carcinogens in cigarette smoke,the role of benzo[a]pyrene(BaP)in prostate cancer is still unclear.The current study aimed to investgate the impacts of BaP exposure on the progression of PCa towardmalignancy and the regulation of the immune microenvironment.We verified that BaP exposure can promote the proliferation,migration,and apoptosis of prostate cancer cells through in vitro experiments.We constructed a subcutaneous xenograft tumor model of BaP exposure mouse and found that can promote the proliferation of tumors in vivo.Organoids-driven by PCa patients showed higher growth rate under BaP exposure.Flow cytometric analysis demonstrated a remarkable decrease in CD4^(+)T and CD8^(+)T cell infiltration levels.Moreover,we identified four genes(Mdm2,Ar,Foxo1,Crebbp)were strongly associated with BaP exposure by combining mouse tumor RNA-seq and CTD database.Additionally,a nomogram integrating clinicopathological features was constructed to assess the prognosis of prostate cancer patients under BaP exposure.This study systematically proved that BaP exposure promotes malignant progression of PCa and suppresses the immune microenvironment,in which Mdm2,Ar,Foxo1,Crebbp may play a crucial role in inhibiting apoptosis.These findings offer novel insights into themechanisms via which BaP exposure contributes to PCa development.
基金supported in part by the National Natural Science Foundation of China(No.82002923,82203505).
文摘Interferon regulatory factors(IRFs)are transcription factors with a conserved N-terminal helix-loop-helix DNA-binding domain 1.IRF family plays a pivotal role in regulating interferon transcription,immune cell development,cell growth,apoptosis,and oncogenesis.2 Despite considerable research,the roles of IRFs in cancer development,metastasis,drug resistance,and prognosis remain unclear.Through multidimensional correlation analysis,we examined the association between IRFs and various cancer characteristics,including clinical and immune subtype analysis,stemness,tumor microenvironment(TME),and drug sensitivity,by utilizing The Cancer Genome Atlas(TCGA)data.Moreover,the classification and prognostic role of IRF1 were further validated through immunohistochemistry staining of kidney renal papillary cell carcinoma(KIRP)clinical tissues.This research enriches our understanding of the IRFs’roles in cancer and their clinical applications.
