Exploring the molecular mechanisms and therapeutic potential of SMAD4 in colorectal cancer

Cancer Biology & Therapy, Год журнала: 2024, Номер 25(1)

Опубликована: Авг. 20, 2024

Colorectal Cancer (CRC) is the third most common cancer worldwide, and occurrence development of CRC are influenced by molecular biology characteristics CRC, especially alterations in key signaling pathways. The transforming growth factor-β (TGF-β) plays a crucial role cellular growth, differentiation, migration, apoptosis, with SMAD4 protein serving as transcription factor TGF-β pathway, thus playing significant onset progression CRC. one malignancies high mortality rate worldwide. Despite research progress recent years, regarding SMAD4, its dual early late stages tumor has promoted further discussion on complexity therapeutic target, highlighting urgent need for deeper analysis This review aims to explore function potential target.

Язык: Английский

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Interactions between NAD+ metabolism and immune cell infiltration in ulcerative colitis: subtype identification and development of novel diagnostic models

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 5, 2025

Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa with increasing incidence worldwide. Growing evidence highlights pivotal role nicotinamide adenine dinucleotide (NAD+) metabolism in UC pathogenesis, prompting our investigation into subtype-specific molecular underpinnings and diagnostic potential NAD+ metabolism-related genes (NMRGs). Transcriptome data from patients healthy controls were downloaded GEO database, specifically GSE75214 GSE87466. We performed unsupervised clustering based on differentially expressed (DE-NMRGs) to classify cases distinct subtypes. GSEA GSVA identified biological pathways active within these subtypes, while CIBERSORT algorithm assessed differential immune cell infiltration. Weighted gene co-expression network analysis (WGCNA) combined expression was used pinpoint specific NMRGs UC. Robust features for subtyping diagnosis selected using two machine learning algorithms. Nomograms constructed their effectiveness evaluated receiver operating characteristic (ROC) curves. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) conducted verify lines. In study, classified subtypes DE-NMRGs levels, Cluster A exhibiting enhanced self-repair capabilities during responses B showing greater inflammation tissue damage. Through comprehensive bioinformatics analyses, we four key biomarkers (AOX1, NAMPT, NNMT, PTGS2) subtyping, (NNMT, PARP9) its diagnosis. These are closely linked various cells microenvironment, particularly NAMPT PTGS2, which strongly associated neutrophil developed demonstrated high predictive accuracy, achieving area under curve (AUC) values up 0.989 0.997 training set 0.998 0.988 validation sets. RT-qPCR showed significant upregulation NNMT PARP9 inflamed versus normal epithelia, underscoring relevance. Our study reveals UC, identifying findings could suggest therapeutic targets contribute advancing personalized treatment strategies potentially improving patient outcomes.

Язык: Английский

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Gene expression regulation and polyadenylation in ulcerative colitis via long-chain RNA sequencing

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 15, 2025

Ulcerative colitis (UC) is an immune-mediated chronic intestinal disease, with a pathogenesis that remains incompletely understood. The purpose of this study to analyze the difference gene expression between UC patients and healthy controls using Oxford Nanopore Technology's long-read RNA sequencing (ONT-RNA-seq) explore how alternative polyadenylation (APA) site selection contributes pathogenesis. Colon tissue samples from normal (NC) were collected, total was extracted sequenced ONT-RNA-seq technology. Various bioinformatics analyses performed, including differential (DEG) analysis, functional enrichment APA prediction miRNAs binding proteins (RBPs) targets, molecular mechanism underlying UC. analysis revealed levels ACSF2, NPY, SLC26A3, BRINP3, PKLPP2 significantly lower in compared NC group, while CCL20, CCL21, CD55, IDO1, LCN2, NOS2, CCL11, OLFM4, ANXA1, REG1A, S100A9, SLPI, SPINK1, AGR2 higher. Functional showed DEGs closely related immune inflammatory responses, which turn are many challenges diagnosis treatment Mechanistically, found contribute regulation UC, some genes identified as potential regulators RBPs. Vene diagram significant overlap miRNA- RBP-targeted DEGs, suggesting may modulate through miRNA RBP targeting. Additionally, five key genes——CD38, NCALD, SMIM31, GPX7, SWAP70——were potentially playing crucial role This provides new insights into mechanisms technology, especially selection.

Язык: Английский

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Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

Egyptian Journal of Medical Human Genetics, Год журнала: 2025, Номер 26(1)

Опубликована: Март 4, 2025

Abstract Background Huntington's disease (HD) could cause progressive motor deficits, psychiatric symptoms, and cognitive impairment. With the increasing use of pharmacotherapies theoretically target neurotransmitters, incidence HD is still not decreasing. However, molecular pathogenesis have been illuminate. It momentous to further examine HD. Methods The next generation sequencing dataset GSE105041 was downloaded from Gene Expression Omnibus (GEO) database. Using DESeq2 in R bioconductor package screen differentially expressed genes (DEGs) between samples normal control samples. ontology (GO) term REACTOME pathway enrichment were performed on DEGs. Meanwhile, using Integrated Interactions Database (IID) database Cytoscape software construct protein–protein interaction (PPI) network module analysis, identify hub with highest value node degree, betweenness, stress closeness scores. miRNA-hub gene regulatory TF-hub constructed analyzed. Receiver operating characteristic curves analysis for diagnostic genes. Results We identified 958 DEGs, consisting 479 up regulated DEGs down GO terms analyses by g:Profiler online results revealed that mainly enriched multicellular organismal process, developmental signaling GPCR MHC class II antigen presentation. Network Analyzer plugin PPI network, LRRK2, MTUS2, HOXA1, IL7R, ERBB3, EGFR, TEX101, WDR76, NEDD4L COMT selected as Hsa-mir-1292-5p, hsa-mir-4521, ESRRB SREBF1 are potential biomarkers predicted be associated Conclusion This study investigated key pathways interactions its complications, which might help reveal correlation complications. current investigation captured prediction, follow-up biological experiments enforced validation.

Язык: Английский

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Characterizing macrophage diversity in colorectal malignancies through single-cell genomics

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 21, 2025

Colorectal cancer (CRC) is one of the most common malignant tumors digestive tract, with increasing incidence and mortality rates, posing a significant burden on human health. Its progression relies various mechanisms, among which tumor microenvironment tumor-associated macrophages (TAMs) have garnered attention. Macrophage infiltration in solid associated poor prognosis linked to chemotherapy resistance many cancers. These biological behaviors depend heterogeneity macrophages. Tumor-promoting TAMs comprise subpopulations characterized by distinct markers unique transcriptional profiles, rendering them potential targets for anticancer therapies through either depletion or reprogramming from pro-tumoral an anti-tumoral state. Single-cell RNA sequencing technology has significantly enhanced our research resolution, breaking traditional simplistic definitions macrophage subtypes deepening understanding diversity within TAMs. However, unified elucidation nomenclature molecular characteristics this remains lacking. In review, we assess application conventional polarization colorectal malignancies explore several defined single-cell omics perspective recent years, categorizing based their functions.

Язык: Английский

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CCL20-CCR6 signaling in tumor microenvironment: Functional roles, mechanisms, and immunotherapy targeting

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер unknown, С. 189341 - 189341

Опубликована: Май 1, 2025

Язык: Английский

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The chemokine CCL20 promotes hepatocyte cholesterol deposition during metabolic dysfunction-associated steatohepatitis by regulating OLR1 expression

Metabolism, Год журнала: 2025, Номер unknown, С. 156301 - 156301

Опубликована: Май 1, 2025

Язык: Английский

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Silencing SMAD4 inhibits inflammation and ferroptosis in asthma by blocking the IL-17A signaling pathway

Respiratory Research, Год журнала: 2024, Номер 25(1)

Опубликована: Дек. 6, 2024

The TGF-β/SMAD signaling pathway is crucial in the pathogenesis of asthma. However, SMAD family member 4 (SMAD4), a key mediator TGF-β, its roles and underlying mechanisms asthma remain unclear. vivo vitro SMAD4 were investigated through an ovalbumin (OVA)-induced mouse model interleukin-13 (IL-13)-induced cell model. molecular mechanism influenced was examined using transcriptome sequencing, followed by feedback experiments involving recombinant human interleukin 17 A (rhIL-17 A), IL-17 activator. highly expressed models. silencing alleviated damage to lung tissue decreased inflammatory infiltration. Expression levels Caspase-3, IgG, factors reduced after SMAD4. Silencing suppressed ferroptosis. also enhanced IL-13-induced BEAS-2B proliferation apoptosis. Furthermore. promoted models, as evidenced elevated IL-17RA, A, Act1 protein levels. inhibited expression these pathway-associated proteins. Moreover, rhIL-17 treatment notably reversed impacts on OVA-induced model, indicating that inflammation ferroptosis blocking pathway. prevents inhibiting pathway, which provides novel potential approach for therapy.

Язык: Английский

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Progress of CCL20-CCR6 in the airways: a promising new therapeutic target

Journal of Inflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Дек. 27, 2024

The chemokine CCL20, a small cytokine that belongs to the C–C family, interacts with its homologous receptor CCR6, which is expressed on wide range of cell types. According current research, CCL20-CCR6 has been established as acritical player in diverse inflammatory, oncogenic, and autoimmune diseases. Within respiratory system, demonstrates heightened expression conditions such allergic asthma, chronic airway inflammation, non-small lung cancer (NSCLC), obstructive pulmonary disease (COPD), other diseases, conducive inflammatory mediators recruitment tumor microenvironment remodeling. Numerous studies have demonstrated therapeutic interventions targeting CCL20 including antibodies antagonists, potential mitigate progression. Despite promising research prospects surrounding axis, precise mechanisms underlying action diseases remain largely elusive. In this review, we delve into roles axis within system by synthesizing analyzing findings. Our objective provide comprehensive understanding implications for health disease. And aspire propel endeavors domain furnish valuable insights development future strategies.

Язык: Английский

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Time‐series transcriptome reveals inflammatory signature in monocytes and neutrophils following acute heat exposure in mine rescuers

Physiological Reports, Год журнала: 2024, Номер 12(3)

Опубликована: Фев. 1, 2024

Abstract Occupational exposure to extreme high temperatures and the increasing global necessitates a deeper understanding of impact heat on human health. However, molecular mechanisms underlying response monocytes neutrophils in occupational population remain be fully elucidated. This study used longitudinal transcriptome assess acute (50°C for 30 min) 10 subjects from mine rescue team before (baseline) at 5 min, 1 h, 24 h after (recovery). The time‐series analysis revealed coordinated choreography changes involving inflammation, coagulation, extracellular matrix, energy metabolism. Importantly, characterized inflammatory signature associated with neutrophils, as evidenced by rapid activation inflammation‐related following exposure. Additionally, we pinpointed potential regulators, such NR4A1, FOSL1, EGR3, ATF3. In summary, suggested that initial stress member was primarily pro‐inflammatory response, which could potentially lead development inflammation ultimately result systemic heatstroke.

Язык: Английский

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