Aim:This study aims to investigate the expression of the Ankyrin Repeat Domain 6(ANKRD6)gene in Colon Adenocarcinoma(COAD)and its regulatory role in key signaling pathways,evaluating its clinical value as a potential ...Aim:This study aims to investigate the expression of the Ankyrin Repeat Domain 6(ANKRD6)gene in Colon Adenocarcinoma(COAD)and its regulatory role in key signaling pathways,evaluating its clinical value as a potential therapeutic target.Methods:To investigate the functional role of ANKRD6 in colon adenocarcinoma(COAD),we systematically analyzed its prognostic relevance,epigenetic regulation,and association with tumor stemness using publicly available TCGA(The Cancer Genome Atlas)-COAD data.Gene set variation analysis(GSVA)was applied to identify signaling pathways potentially modulated by ANKRD6.Least Absolute Shrinkage and Selection Operator(LASSO)regression was employed to identify key genes within the Wnt signaling pathway that are significantly associated with COAD patient survival.Immunohistochemical staining was performed to confirm ANKRD6 protein expression in COAD tissues.To investigate functional consequences,ANKRD6 was knocked down using small interfering RNAs,and subsequent quantitative real-time polymerase chain reaction and Western blot assays were applied to measure alterations in representative Wnt pathway-related genes and proteins.Results:ANKRD6 expression was significantly associated with DNA methylation patterns,RNA modification regulators,and tumor stemness features in COAD.These findings suggest that epigenetic and post-transcriptional mechanisms may underlie the regulatory role of ANKRD6 in COAD pathogenesis.GSVA analysis revealed that ANKRD6 significantly influences and negatively regulates Wnt signaling pathway activity.LASSO regression analysis highlighted 25 Wnt pathway genes relevant to COAD patient survival,with ANKRD6 expression significantly correlated with multiple targets.Furthermore,immunohistochemical staining confirmed that ANKRD6 protein was markedly upregulated in COAD tissues.Upon ANKRD6 knockdown,the messenger RNA levels of WNT7A(Wnt Family Member 7A),JNK(Mitogen-Activated Protein Kinase 8),and RHOA(Ras Homolog Family Member A),as well as WNT7A protein levels,showed a significant decrease in the Wnt signaling pathway.Conclusions:ANKRD6 plays a critical role in the development and progression of COAD by regulating the Wnt signaling pathway.It holds potential as a therapeutic target,warranting further investigation into its specific regulatory mechanisms and clinical applications.展开更多
Objectives:Allergic rhinitis(AR)refers to a form of respiratory inflammation that mainly affects the sinonasal mucosa.The purpose of this study was to explore the level of immune cell infiltration and the pathogenesis...Objectives:Allergic rhinitis(AR)refers to a form of respiratory inflammation that mainly affects the sinonasal mucosa.The purpose of this study was to explore the level of immune cell infiltration and the pathogenesis of AR.Methods:We performed a comprehensive analysis of two gene expression profiles(GSE50223 and GSE50101,a total of 30 patients with AR and 31 healthy controls).CIBERSORT was used to evaluate the immune cell infiltration levels.Weighted gene coexpression network analysis was applied to explore potential genes or gene modules related to immune status,and enrichment analyses including gene ontology,Kyoto Encyclopedia of Genes and Genomes,gene set enrichment analysis,and gene set variation analysis,were performed to analyze the potential mechanisms in AR.A protein–protein interaction network was constructed to investigate the hub genes,and consensus clustering was conducted to identify the molecular subtypes of AR.Results:Compared to the healthy controls,patients with AR had high abundance levels and proportions of CD4+memory‐activated T cells.One hundred and eight immune‐related differentially expressed genes were identified.Enrichment analysis suggested that AR was mainly related to leukocyte cell‐cell adhesion,cytokine‐cytokine receptor interaction,T‐cell activation,and T‐cell receptor signaling pathway.Ten hub genes,includingTYROBP,CSF1R,TLR8,FCER1G,SPI1,ITGAM,CYBB,FCGR2A,CCR1,andHCK,which were related to immune response,might be crucial to the pathogenesis of AR.Three molecular subtypes with significantly different immune statuses were identified.Conclusion:This study improves our understanding of the molecular mechanisms in AR via comprehensive strategies and provides potential diagnostic biomarkers and therapeutic targets of AR.展开更多
基金supported by the following grants:the 2023 Anhui Provincial Health and Wellness Research Project(Grant No.AHWJ2023Bba20065)the Anhui Province Clinical Medicine Research and Transformation Program(Grant No.202427b10020034)+1 种基金the 2024 University-Enterprise Integrated Development“Qilu Research Fund”Project(Grant No.XQQL202408)the 2024 Key Research Project Fund(Natural Sciences Category)(Grant No.WK2024ZZD28).
文摘Aim:This study aims to investigate the expression of the Ankyrin Repeat Domain 6(ANKRD6)gene in Colon Adenocarcinoma(COAD)and its regulatory role in key signaling pathways,evaluating its clinical value as a potential therapeutic target.Methods:To investigate the functional role of ANKRD6 in colon adenocarcinoma(COAD),we systematically analyzed its prognostic relevance,epigenetic regulation,and association with tumor stemness using publicly available TCGA(The Cancer Genome Atlas)-COAD data.Gene set variation analysis(GSVA)was applied to identify signaling pathways potentially modulated by ANKRD6.Least Absolute Shrinkage and Selection Operator(LASSO)regression was employed to identify key genes within the Wnt signaling pathway that are significantly associated with COAD patient survival.Immunohistochemical staining was performed to confirm ANKRD6 protein expression in COAD tissues.To investigate functional consequences,ANKRD6 was knocked down using small interfering RNAs,and subsequent quantitative real-time polymerase chain reaction and Western blot assays were applied to measure alterations in representative Wnt pathway-related genes and proteins.Results:ANKRD6 expression was significantly associated with DNA methylation patterns,RNA modification regulators,and tumor stemness features in COAD.These findings suggest that epigenetic and post-transcriptional mechanisms may underlie the regulatory role of ANKRD6 in COAD pathogenesis.GSVA analysis revealed that ANKRD6 significantly influences and negatively regulates Wnt signaling pathway activity.LASSO regression analysis highlighted 25 Wnt pathway genes relevant to COAD patient survival,with ANKRD6 expression significantly correlated with multiple targets.Furthermore,immunohistochemical staining confirmed that ANKRD6 protein was markedly upregulated in COAD tissues.Upon ANKRD6 knockdown,the messenger RNA levels of WNT7A(Wnt Family Member 7A),JNK(Mitogen-Activated Protein Kinase 8),and RHOA(Ras Homolog Family Member A),as well as WNT7A protein levels,showed a significant decrease in the Wnt signaling pathway.Conclusions:ANKRD6 plays a critical role in the development and progression of COAD by regulating the Wnt signaling pathway.It holds potential as a therapeutic target,warranting further investigation into its specific regulatory mechanisms and clinical applications.
基金Beijing Health Technologies Promotion Program(Grant/Award Number:BHTPP202007)Research and Development Foundation of Peking University People’s Hospital(Grant/Award Number:RDL2021‐05)Capital Health Research and Development of Special Fund(Grant/Award Number:2020‐1‐2051)。
文摘Objectives:Allergic rhinitis(AR)refers to a form of respiratory inflammation that mainly affects the sinonasal mucosa.The purpose of this study was to explore the level of immune cell infiltration and the pathogenesis of AR.Methods:We performed a comprehensive analysis of two gene expression profiles(GSE50223 and GSE50101,a total of 30 patients with AR and 31 healthy controls).CIBERSORT was used to evaluate the immune cell infiltration levels.Weighted gene coexpression network analysis was applied to explore potential genes or gene modules related to immune status,and enrichment analyses including gene ontology,Kyoto Encyclopedia of Genes and Genomes,gene set enrichment analysis,and gene set variation analysis,were performed to analyze the potential mechanisms in AR.A protein–protein interaction network was constructed to investigate the hub genes,and consensus clustering was conducted to identify the molecular subtypes of AR.Results:Compared to the healthy controls,patients with AR had high abundance levels and proportions of CD4+memory‐activated T cells.One hundred and eight immune‐related differentially expressed genes were identified.Enrichment analysis suggested that AR was mainly related to leukocyte cell‐cell adhesion,cytokine‐cytokine receptor interaction,T‐cell activation,and T‐cell receptor signaling pathway.Ten hub genes,includingTYROBP,CSF1R,TLR8,FCER1G,SPI1,ITGAM,CYBB,FCGR2A,CCR1,andHCK,which were related to immune response,might be crucial to the pathogenesis of AR.Three molecular subtypes with significantly different immune statuses were identified.Conclusion:This study improves our understanding of the molecular mechanisms in AR via comprehensive strategies and provides potential diagnostic biomarkers and therapeutic targets of AR.
