Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-...Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.展开更多
Background:In regard to head and neck squamous cell carcinoma(HNSC),a common type of head and neck malignant tumor with high mortality,the role of Piezo-type mechanosensitive ion channel component 1(PIEZO1)is poorly u...Background:In regard to head and neck squamous cell carcinoma(HNSC),a common type of head and neck malignant tumor with high mortality,the role of Piezo-type mechanosensitive ion channel component 1(PIEZO1)is poorly understood.PIEZO1,a mechanosensitive ion channel,is implicated in tumorigenesis,but its expression,prognostic significance,and mechanisms in HNSC remain unclear.Our study aimed to clarify these aspects through in vitro experiments and bioinformatics analyses.Methods:In order to investigate PIEZO1 expression in normal and cancerous tissues,we used The Cancer Genome Atlas data.Our bioinformatics analyses explored PIEZO1 mRNA expression,correlations,survival curves,upstream mRNA targets,and coexpressed genes.Gene Ontology analysis functionally annotated these coexpressed genes,and pathway enrichment studies further clarified their roles.In addition,we conducted in vitro experiments to examine and compare PIEZO1 expression in normal and cancerous human tissue samples.We performed immunohistochemical analyses to detect PIEZO1 expression in human HNSC tissues.Results:Our results have revealed significantly elevated PIEZO1 expression in HNSC tissue samples compared with adjacent noncancerous tissues.Bioinformatics analysis further showed that PIEZO1 expression was notably higher in high-grade HNSC tumors and was associated with lower survival rates.OncomiR database analysis showed that the downregulation of hsa-miR-101-3p correlated with increased PIEZO1 expression in HNSC.Mechanistic studies identified 4 focal adhesion-related genes(ITGA5,LAMC2,PXN,and VEGFC)modulated by PIEZO1.These findings underscore the potential of PIEZO1 as a therapeutic target and prognostic marker for HNSC.Conclusions:Our study has revealed the expression profile of PIEZO1 in HNSC,emphasizing its potential as a diagnostic and therapeutic target along with hsa-miR-101-3p.展开更多
基金funded by the Natural Science Foundation of Guangdong Province(grant number 2022A1515012315)Guangdong Medical Science and Technology Research Fund Project(grant number A2023185)+2 种基金the Discipline Construction Project of Guangdong Medical University(grant number 4SG22005G)the 2023 Provincial Basic and Applied Basic Research Fund Enterprise Joint Fund Project(grant number 2023A1515220149)Southern Medical University Shunde Hospital 2023 Research Initiation Programme Project(SRSP2023016).
文摘Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.
基金supported by grants from Hefei Municipal Health Commission,Hefei Municipal Finance Bureau(No.[2023]72).
文摘Background:In regard to head and neck squamous cell carcinoma(HNSC),a common type of head and neck malignant tumor with high mortality,the role of Piezo-type mechanosensitive ion channel component 1(PIEZO1)is poorly understood.PIEZO1,a mechanosensitive ion channel,is implicated in tumorigenesis,but its expression,prognostic significance,and mechanisms in HNSC remain unclear.Our study aimed to clarify these aspects through in vitro experiments and bioinformatics analyses.Methods:In order to investigate PIEZO1 expression in normal and cancerous tissues,we used The Cancer Genome Atlas data.Our bioinformatics analyses explored PIEZO1 mRNA expression,correlations,survival curves,upstream mRNA targets,and coexpressed genes.Gene Ontology analysis functionally annotated these coexpressed genes,and pathway enrichment studies further clarified their roles.In addition,we conducted in vitro experiments to examine and compare PIEZO1 expression in normal and cancerous human tissue samples.We performed immunohistochemical analyses to detect PIEZO1 expression in human HNSC tissues.Results:Our results have revealed significantly elevated PIEZO1 expression in HNSC tissue samples compared with adjacent noncancerous tissues.Bioinformatics analysis further showed that PIEZO1 expression was notably higher in high-grade HNSC tumors and was associated with lower survival rates.OncomiR database analysis showed that the downregulation of hsa-miR-101-3p correlated with increased PIEZO1 expression in HNSC.Mechanistic studies identified 4 focal adhesion-related genes(ITGA5,LAMC2,PXN,and VEGFC)modulated by PIEZO1.These findings underscore the potential of PIEZO1 as a therapeutic target and prognostic marker for HNSC.Conclusions:Our study has revealed the expression profile of PIEZO1 in HNSC,emphasizing its potential as a diagnostic and therapeutic target along with hsa-miR-101-3p.
