Objectives:Non-small cell lung cancer(NSCLC)represents a formidable malignancy characterized by its marked metastatic potential and intrinsic resistance to therapeutic interventions.The identification of potential bio...Objectives:Non-small cell lung cancer(NSCLC)represents a formidable malignancy characterized by its marked metastatic potential and intrinsic resistance to therapeutic interventions.The identification of potential biomarkers delineating the progression and metastatic cascade of NSCLC assumes paramount importance in fostering advancements toward enhanced patient outcomes and prognostic stratification.Methods:The expression level of the actin-related protein 2/3 complex;subunit 1A(ARPC1A)in NSCLC was evaluated using The Cancer Genome Atlas(TCGA)and Gene Expression Profiling Interactive Analysis(GEPIA)databases;along with the LinkedOmics database for co-expression genes.Further verification of ARPC1A expression in normal lung cells and NSCLC cells;as well as in normal tissues and lung cancer tissues;was performed using quantitative real-time reverse transcription PCR(RTqPCR)and Western blotting.The function of ARPC1A was explored through Gene Set Enrichment Analysis(GSEA)and immune infiltration analysis;followed by functional experiments for validation.Results:ARPC1A is upregulated in NSCLC and is associated with unfavorable clinical prognoses.Additionally,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis highlights a potential link between the ARPC1A gene and the cell cycle and p53 signaling pathways.ARPC1A also promotes cell proliferation and resistance to chemotherapeutic drugs,thereby enhancing the oncogenic potential of NSCLC.Relevant cell-based experiments confirm that targeted inhibition of ARPC1A effectively suppresses cellular migratory and invasive capabilities.The immune infiltration analysis showed a close association between ARPC1A expression and various immune components,suggesting ARPC1A may interact with the tumor microenvironment.Mechanistically,ARPC1A promotes cell migration by stimulating the epithelialto-mesenchymal transition(EMT).Conclusion:The study results revealed the potential of ARPC1A as a valuable prognostic biomarker for NSCLC.Additionally,the associated mechanisms provide insights that may pave the way for therapeutic interventions for NSCLC patients.展开更多
Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protei...Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B(ARPC1B),a key regulatory protein within the actin cytoskeleton,could play a pivotal role in ccRCC progression.The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC.Methods:ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,immunohistochemical(IHC)staining on 150 tumor samples along with 30 corresponding normal tissues,and Western blotting(WB)analyses across multiple ccRCC-derived cell lines.Functional assays assessing cell proliferation,colony formation capability,migration,invasion,and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation.Additionally,WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition(EMT)and the Wnt/β-catenin pathway.Results:The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines,significantly associated with advanced TNM stages,higher Fuhrman grades,and reduced overall survival(OS)(p<0.001).Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor.Silencing ARPC1B notably impaired ccRCC cellular activities,and tumorigenesis in animalmodels,whereas augmented ARPC1B expression enhanced these malignant phenotypes.Mechanistically,downregulation of ARPC1B suppressed Wnt/β-catenin signaling and disrupted EMT,indicated by reducedβ-catenin,c-Myc,cyclin D1,and ZEB-1 levels,and concurrently increased E-cadherin expression.Additionally,reactivation of theWnt/β-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness.Conclusions:ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/β-catenin pathway,ultimately enhancing tumor aggressiveness and metastatic potential.Thus,targeting ARPC1B represents a promising therapeutic strategy,warranting further exploration in ccRCC management.展开更多
Cytoskeletal network dysregulation is a pivotal determinant in various immunodeficiencies and autoinflammatory conditions. This report reviews the significance of actin remodeling in disease pathogenesis, focusing on ...Cytoskeletal network dysregulation is a pivotal determinant in various immunodeficiencies and autoinflammatory conditions. This report reviews the significance of actin remodeling in disease pathogenesis, focusing on the Arp2/3 complex and its regulatory subunit actin related protein 2/3 complex subunit 1B (ARPC1B). A spectrum of cellular dysfunctions associated with ARPC1B deficiency, impacting diverse immune cell types, is elucidated. The study presents a patient featuring recurrent and persistent eosinophilia attributed to homozygous ARPC1B mutation alongside concomitant compound heterozygous cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. We used ARPC1B antibody to stain the patient’s peripheral blood lymphocytes and those of the control. The defect in the ARPC1B gene in the present patient caused absent/low expression by immunofluorescence microscopy. The intricate interplay between cytoskeletal defects and immunological manifestations underscores the complexity of disease phenotypes, warranting further exploration for targeted therapeutic strategies.展开更多
基金supported by the Natural Science Foundation of Anhui Province(ML 2308085MC80)the Anhui Medical University Research and Innovation Talent Team(KZ).
文摘Objectives:Non-small cell lung cancer(NSCLC)represents a formidable malignancy characterized by its marked metastatic potential and intrinsic resistance to therapeutic interventions.The identification of potential biomarkers delineating the progression and metastatic cascade of NSCLC assumes paramount importance in fostering advancements toward enhanced patient outcomes and prognostic stratification.Methods:The expression level of the actin-related protein 2/3 complex;subunit 1A(ARPC1A)in NSCLC was evaluated using The Cancer Genome Atlas(TCGA)and Gene Expression Profiling Interactive Analysis(GEPIA)databases;along with the LinkedOmics database for co-expression genes.Further verification of ARPC1A expression in normal lung cells and NSCLC cells;as well as in normal tissues and lung cancer tissues;was performed using quantitative real-time reverse transcription PCR(RTqPCR)and Western blotting.The function of ARPC1A was explored through Gene Set Enrichment Analysis(GSEA)and immune infiltration analysis;followed by functional experiments for validation.Results:ARPC1A is upregulated in NSCLC and is associated with unfavorable clinical prognoses.Additionally,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis highlights a potential link between the ARPC1A gene and the cell cycle and p53 signaling pathways.ARPC1A also promotes cell proliferation and resistance to chemotherapeutic drugs,thereby enhancing the oncogenic potential of NSCLC.Relevant cell-based experiments confirm that targeted inhibition of ARPC1A effectively suppresses cellular migratory and invasive capabilities.The immune infiltration analysis showed a close association between ARPC1A expression and various immune components,suggesting ARPC1A may interact with the tumor microenvironment.Mechanistically,ARPC1A promotes cell migration by stimulating the epithelialto-mesenchymal transition(EMT).Conclusion:The study results revealed the potential of ARPC1A as a valuable prognostic biomarker for NSCLC.Additionally,the associated mechanisms provide insights that may pave the way for therapeutic interventions for NSCLC patients.
文摘Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B(ARPC1B),a key regulatory protein within the actin cytoskeleton,could play a pivotal role in ccRCC progression.The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC.Methods:ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,immunohistochemical(IHC)staining on 150 tumor samples along with 30 corresponding normal tissues,and Western blotting(WB)analyses across multiple ccRCC-derived cell lines.Functional assays assessing cell proliferation,colony formation capability,migration,invasion,and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation.Additionally,WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition(EMT)and the Wnt/β-catenin pathway.Results:The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines,significantly associated with advanced TNM stages,higher Fuhrman grades,and reduced overall survival(OS)(p<0.001).Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor.Silencing ARPC1B notably impaired ccRCC cellular activities,and tumorigenesis in animalmodels,whereas augmented ARPC1B expression enhanced these malignant phenotypes.Mechanistically,downregulation of ARPC1B suppressed Wnt/β-catenin signaling and disrupted EMT,indicated by reducedβ-catenin,c-Myc,cyclin D1,and ZEB-1 levels,and concurrently increased E-cadherin expression.Additionally,reactivation of theWnt/β-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness.Conclusions:ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/β-catenin pathway,ultimately enhancing tumor aggressiveness and metastatic potential.Thus,targeting ARPC1B represents a promising therapeutic strategy,warranting further exploration in ccRCC management.
文摘Cytoskeletal network dysregulation is a pivotal determinant in various immunodeficiencies and autoinflammatory conditions. This report reviews the significance of actin remodeling in disease pathogenesis, focusing on the Arp2/3 complex and its regulatory subunit actin related protein 2/3 complex subunit 1B (ARPC1B). A spectrum of cellular dysfunctions associated with ARPC1B deficiency, impacting diverse immune cell types, is elucidated. The study presents a patient featuring recurrent and persistent eosinophilia attributed to homozygous ARPC1B mutation alongside concomitant compound heterozygous cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. We used ARPC1B antibody to stain the patient’s peripheral blood lymphocytes and those of the control. The defect in the ARPC1B gene in the present patient caused absent/low expression by immunofluorescence microscopy. The intricate interplay between cytoskeletal defects and immunological manifestations underscores the complexity of disease phenotypes, warranting further exploration for targeted therapeutic strategies.
