Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study ...Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study aimed to explore the specific mechanism by which microRNA-409-5p(miR-409-5p)contributes to GIST.Methods To identify genes potentially involved in the development and progression of GIST,the differences of miR-409-5p between tumors and adjacent tissues were first analyzed.Following this analysis,target genes were predicted.To further investigate the function of miRNA in GIST cells,two GIST cell lines(GIST-T1 and GIST882)were transfected with lentiviruses that stably expressed miR-409-5p and scrambled miRNA(negative control).Later,the cells were subjected to Western blotting and ELSA to determine any differences in angiogenesis-related genes.Results In GISTs,there was a decrease in the expression levels of miR-409-5p compared to the adjacent tissues.It was observed that the upregulation of miR-409-5p in GIST cell lines effectively inhibited the proteins hypoxia-inducible transcription factor 1β(HIF1β)and vascular endothelial growth factor A(VEGF-A).Further investigations revealed that miR-409-5p acted as an inhibitor of angiogenesis by binding to the 3′-UTR of Lysine-specific demethylase 4D(KDM4D)mRNA.Moreover,the combination of miR-409-5p with imatinib enhanced its inhibitory effect on angiogenesis.Conclusion This study demonstrated that the miRNA-409-5p/KDM4D/HIF1β/VEGF-A signaling pathway could serve as a novel target for the development of therapeutic strategies for the treatment of imatinib-resistance in GIST patients.展开更多
Colorectal cancer(CRC)considerably affects global health,and its progression is intricately tied to interactions within the tumormicroenvironment.This review focuses on the intricate crosstalk between metabolic reprog...Colorectal cancer(CRC)considerably affects global health,and its progression is intricately tied to interactions within the tumormicroenvironment.This review focuses on the intricate crosstalk between metabolic reprogramming in CRC cells and the tumor immune microenvironment(TIME),thereby emphasizing the dual functionality of metabolic pathways in tumor growth and immune regulation.Furthermore,the review delves into key metabolic changes,including alterations in glucose,lipid,iron,and ammonia metabolism,and their profound effects on the immune landscape of CRC.Enhanced glycolysis and lipid metabolism facilitate tumor survival and proliferation,while establishing an immunosuppressive TIME that hinders effective immune responses.Moreover,the roles of iron and ammonia metabolism in immune evasion and tumor progression were explored,and these metabolic pathways presented as promising targets to improve CRC therapy.By conducting a comprehensive analysis of recent studies,this review provides insights into potential therapeutic targets within these metabolic interactions,with the aim of enhancing the efficacy of existing treatments and devising novel strategies for combating CRC.展开更多
Objective Kidney renal clear cell carcinoma(KIRC)is a common renal malignancy that has a poor prognosis.As a member of the F box family,cyclin F(CCNF)plays an important regulatory role in normal tissues and tumors.How...Objective Kidney renal clear cell carcinoma(KIRC)is a common renal malignancy that has a poor prognosis.As a member of the F box family,cyclin F(CCNF)plays an important regulatory role in normal tissues and tumors.However,the underlying mechanism by which CCNF promotes KIRC proliferation still remains unclear.Methods Bioinformatics methods were used to analyze The Cancer Genome Atlas(TCGA)database to obtain gene expression and clinical prognosis data.The CCK8 assay,EdU assay,and xenograft assay were used to detect cell proliferation.The cell senescence and potential mechanism were assessed by SA-β-gal staining,Western blotting,as well as ELISA.Results Our data showed that CCNF was highly expressed in KIRC patients.Meanwhile,downregulation of CCNF inhibited cell proliferation in vivo and in vitro.Further studies showed that the reduction of CCNF promoted cell senescence by decreasing cyclin-dependent kinase 1(CDK1),increasing the proinflammatory factors interleukin(IL)-6 and IL-8,and then enhancing the expression of p21 and p53.Conclusion We propose that the high expression of CCNF in KIRC may play a key role in tumorigenesis by regulating cell senescence.Therefore,CCNF shows promise as a new biomarker to predict the clinical prognosis of KIRC patients and as an effective therapeutic target.展开更多
Dynamic DNA nanotechnology plays a significant role in nanomedicine and information science due to its high programmability based on Watson-Crick base pairing and nanoscale dimensions.Intelligent DNA machines and netw...Dynamic DNA nanotechnology plays a significant role in nanomedicine and information science due to its high programmability based on Watson-Crick base pairing and nanoscale dimensions.Intelligent DNA machines and networks have been widely used in various fields,including molecular imaging,biosensors,drug delivery,information processing,and logic operations.Encoders serve as crucial components for information compilation and transfer,allowing the conversion of information from diverse application scenarios into a format recognized and applied by DNA circuits.However,there are only a few encoder designs with DNA outputs.Moreover,the molecular priority encoder is hardly designed.In this study,we introduce allosteric DNAzyme-based encoders for information transfer.The design of the allosteric domain and the recognition arm allows the input and output to be independent of each other and freely programmable.The pre-packaged mode design achieves uniformity of baseline dynamics and dynamics controllability.We also integrated non-nucleic acid molecules into the encoder through the aptamer design of the allosteric domain.Furthermore,we developed the 2^(n)-n encoder and the EndoⅣ-assisted priority encoder inspired by immunoglobulin's molecular structure and effector patterns.To our knowledge,the proposed encoder is the first enzyme-free DNA encoder with DNA output,and the priority encoder is the first molecular priority encoder in the DNA reaction network.Our encoders avoid complex operations on a single molecule,and their simple structure facilitates their application in complex DNA circuits and biological scenarios.展开更多
Emerging data from metabolites-relating trails in cancers demonstrate that a common mechanism of resistance to many novel classes of immune therapeutics is the emergence of immune escape due to the reprogramming of ce...Emerging data from metabolites-relating trails in cancers demonstrate that a common mechanism of resistance to many novel classes of immune therapeutics is the emergence of immune escape due to the reprogramming of cellular metabolism.Among them,current work about end-metabolites mostly focuses on the intersection between lactate acid,adenosine,reactive oxygen species(ROS),and tumour immune escape.In this article,we aim to review the evidence to date for the dynamic interplay between the three end-metabolites and tumour immune escape for potential approaches to overcome obstacles in the efficacy and durability of immune cancer therapies.We have organized known end-metabolites-associated immune escape mechanisms into three hallmarks:(1)decreased immunogenicity of cancer cells which constitutes defective antigen presentation and the attenuated expression of costimulatory molecules on tumour cells,(2)immunosuppressive microenvironment with aberrant angiogenesis inhibits the differentiation,maturation,and immune deviation of immune cells while drives the activation of immunosuppressive cells by immune-suppressive mediators(cytokines and other factors),(3)immune tolerance retained by inhibitory molecules and depletion of immune cells.展开更多
Dear Editor,Malnutrition is a prevalent disease in oncology practice(Arends et al.,2017).With its cancer-specific prevalence ranging from 21%–72%,malnutrition is responsible for 10%–20% cancer deaths(Yin et al.,2021...Dear Editor,Malnutrition is a prevalent disease in oncology practice(Arends et al.,2017).With its cancer-specific prevalence ranging from 21%–72%,malnutrition is responsible for 10%–20% cancer deaths(Yin et al.,2021b).However,malnutrition is often underestimated,misclassified,or left untreated in cancer care(Hébuterne et al.,2014).展开更多
基金supported by the National Natural Science Foundation of China(No.81372323 and No.81802426).
文摘Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study aimed to explore the specific mechanism by which microRNA-409-5p(miR-409-5p)contributes to GIST.Methods To identify genes potentially involved in the development and progression of GIST,the differences of miR-409-5p between tumors and adjacent tissues were first analyzed.Following this analysis,target genes were predicted.To further investigate the function of miRNA in GIST cells,two GIST cell lines(GIST-T1 and GIST882)were transfected with lentiviruses that stably expressed miR-409-5p and scrambled miRNA(negative control).Later,the cells were subjected to Western blotting and ELSA to determine any differences in angiogenesis-related genes.Results In GISTs,there was a decrease in the expression levels of miR-409-5p compared to the adjacent tissues.It was observed that the upregulation of miR-409-5p in GIST cell lines effectively inhibited the proteins hypoxia-inducible transcription factor 1β(HIF1β)and vascular endothelial growth factor A(VEGF-A).Further investigations revealed that miR-409-5p acted as an inhibitor of angiogenesis by binding to the 3′-UTR of Lysine-specific demethylase 4D(KDM4D)mRNA.Moreover,the combination of miR-409-5p with imatinib enhanced its inhibitory effect on angiogenesis.Conclusion This study demonstrated that the miRNA-409-5p/KDM4D/HIF1β/VEGF-A signaling pathway could serve as a novel target for the development of therapeutic strategies for the treatment of imatinib-resistance in GIST patients.
文摘Colorectal cancer(CRC)considerably affects global health,and its progression is intricately tied to interactions within the tumormicroenvironment.This review focuses on the intricate crosstalk between metabolic reprogramming in CRC cells and the tumor immune microenvironment(TIME),thereby emphasizing the dual functionality of metabolic pathways in tumor growth and immune regulation.Furthermore,the review delves into key metabolic changes,including alterations in glucose,lipid,iron,and ammonia metabolism,and their profound effects on the immune landscape of CRC.Enhanced glycolysis and lipid metabolism facilitate tumor survival and proliferation,while establishing an immunosuppressive TIME that hinders effective immune responses.Moreover,the roles of iron and ammonia metabolism in immune evasion and tumor progression were explored,and these metabolic pathways presented as promising targets to improve CRC therapy.By conducting a comprehensive analysis of recent studies,this review provides insights into potential therapeutic targets within these metabolic interactions,with the aim of enhancing the efficacy of existing treatments and devising novel strategies for combating CRC.
基金supported by the National Natural Science Foundation of China(No.81874148 and No.82203142).
文摘Objective Kidney renal clear cell carcinoma(KIRC)is a common renal malignancy that has a poor prognosis.As a member of the F box family,cyclin F(CCNF)plays an important regulatory role in normal tissues and tumors.However,the underlying mechanism by which CCNF promotes KIRC proliferation still remains unclear.Methods Bioinformatics methods were used to analyze The Cancer Genome Atlas(TCGA)database to obtain gene expression and clinical prognosis data.The CCK8 assay,EdU assay,and xenograft assay were used to detect cell proliferation.The cell senescence and potential mechanism were assessed by SA-β-gal staining,Western blotting,as well as ELISA.Results Our data showed that CCNF was highly expressed in KIRC patients.Meanwhile,downregulation of CCNF inhibited cell proliferation in vivo and in vitro.Further studies showed that the reduction of CCNF promoted cell senescence by decreasing cyclin-dependent kinase 1(CDK1),increasing the proinflammatory factors interleukin(IL)-6 and IL-8,and then enhancing the expression of p21 and p53.Conclusion We propose that the high expression of CCNF in KIRC may play a key role in tumorigenesis by regulating cell senescence.Therefore,CCNF shows promise as a new biomarker to predict the clinical prognosis of KIRC patients and as an effective therapeutic target.
基金financially supported by the National Natural Science Foundation of China(No.82172372)the Opening Research Fund of State Key Laboratory of Digital Medical Engineering(No.2023-M04)。
文摘Dynamic DNA nanotechnology plays a significant role in nanomedicine and information science due to its high programmability based on Watson-Crick base pairing and nanoscale dimensions.Intelligent DNA machines and networks have been widely used in various fields,including molecular imaging,biosensors,drug delivery,information processing,and logic operations.Encoders serve as crucial components for information compilation and transfer,allowing the conversion of information from diverse application scenarios into a format recognized and applied by DNA circuits.However,there are only a few encoder designs with DNA outputs.Moreover,the molecular priority encoder is hardly designed.In this study,we introduce allosteric DNAzyme-based encoders for information transfer.The design of the allosteric domain and the recognition arm allows the input and output to be independent of each other and freely programmable.The pre-packaged mode design achieves uniformity of baseline dynamics and dynamics controllability.We also integrated non-nucleic acid molecules into the encoder through the aptamer design of the allosteric domain.Furthermore,we developed the 2^(n)-n encoder and the EndoⅣ-assisted priority encoder inspired by immunoglobulin's molecular structure and effector patterns.To our knowledge,the proposed encoder is the first enzyme-free DNA encoder with DNA output,and the priority encoder is the first molecular priority encoder in the DNA reaction network.Our encoders avoid complex operations on a single molecule,and their simple structure facilitates their application in complex DNA circuits and biological scenarios.
文摘Emerging data from metabolites-relating trails in cancers demonstrate that a common mechanism of resistance to many novel classes of immune therapeutics is the emergence of immune escape due to the reprogramming of cellular metabolism.Among them,current work about end-metabolites mostly focuses on the intersection between lactate acid,adenosine,reactive oxygen species(ROS),and tumour immune escape.In this article,we aim to review the evidence to date for the dynamic interplay between the three end-metabolites and tumour immune escape for potential approaches to overcome obstacles in the efficacy and durability of immune cancer therapies.We have organized known end-metabolites-associated immune escape mechanisms into three hallmarks:(1)decreased immunogenicity of cancer cells which constitutes defective antigen presentation and the attenuated expression of costimulatory molecules on tumour cells,(2)immunosuppressive microenvironment with aberrant angiogenesis inhibits the differentiation,maturation,and immune deviation of immune cells while drives the activation of immunosuppressive cells by immune-suppressive mediators(cytokines and other factors),(3)immune tolerance retained by inhibitory molecules and depletion of immune cells.
基金supported in part by the National Key Research and Development Program(2017YFC1309200)the National Natural Science Foundation of China(81673167)。
文摘Dear Editor,Malnutrition is a prevalent disease in oncology practice(Arends et al.,2017).With its cancer-specific prevalence ranging from 21%–72%,malnutrition is responsible for 10%–20% cancer deaths(Yin et al.,2021b).However,malnutrition is often underestimated,misclassified,or left untreated in cancer care(Hébuterne et al.,2014).
