Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 6743 - 6764
Published: Sept. 1, 2024
Cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression and the development of resistance therapies across a range malignancies, notably breast cancer. This study aims elucidate specific role prognostic relevance CALU multiple cancer types.
Language: Английский
Advanced Science, Journal Year: 2024, Volume and Issue: 11(12)
Published: Jan. 16, 2024
Abstract In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF a well‐established precancerous lesion, portion cases eventually progress squamous cell carcinoma (OSCC). However, specific molecular mechanisms underlying malignant transformation OSCC from are poorly understood. this study, leading‐edge techniques Spatial Transcriptomics (ST) Metabolomics (SM) integrated obtain spatial location information cancer cells, fibroblasts, immune as well transcriptomic metabolomic landscapes in OSF‐derived tissues. This work reveals for first time that some cells undergo partial epithelial–mesenchymal transition (pEMT) within situ (ISC) region, acquiring fibroblast‐like phenotypes participating collagen deposition. Complex interactions among epithelial tumor microenvironment demonstrated. Most importantly, significant metabolic reprogramming OSCC, including abnormal polyamine metabolism, potentially playing pivotal role promoting tumorigenesis evasion discovered. The ST SM data study shed new light on deciphering OSCC. also offers invaluable clues prevention treatment
Language: Английский
Citations
21
Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(2), P. e010782 - e010782
Published: Feb. 1, 2025
Background Advanced triple-negative breast cancer (TNBC) is prone to brain metastasis (BrM). The precise molecular mechanism responsible for this phenomenon has not yet been completely established, so it vital comprehend the behind it. Methods protein chip analysis was conducted identify any abnormal UBE2T expression in TNBC, especially BrM. Here, we used public databases and bioinformatics as well clinical samples from different cohorts investigate interrelationship between UBE2T/CDC42/CD276. This predicted relationship then repeatedly validated using vivo vitro experimental methods. Additionally, multiple approaches were implemented, encompassing western blotting, Co-IP, GST pull-down, flow cytometry, mass spectrometry, immunofluorescence, immunohistochemistry, qRT-PCR reveal of UBE2T-mediated immune escape Results Our results indicate that expressed at elevated levels cancer, negatively linked patient prognosis, BrM TNBC. Data our TCGA a significant correlation immunosuppression. Mechanistically, directly interacts with CDC42, promoting its K48-linked polyubiquitination proteasomal degradation, thereby inhibiting CDC42 degrading CD276 via autophagy-lysosomal pathway, indirectly upregulating impairing CD8 + T cells function, ultimately mediating tumor Finally, animal also showed inhibition TNBC sensitivity checkpoint blockade inhibited Conclusions In conclusion, new whereby ubiquitination positively controls UBE2T/CDC42/CD276 axis upregulate cell impair leading
Language: Английский
Citations
2
Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)
Published: April 15, 2024
Abstract Objective This study aims to investigate the association between specific lipidomes and risk of breast cancer (BC) using Two-Sample Mendelian Randomization (TSMR) approach Bayesian Model Averaging (BMA-MR) method. Method The analyzed data from large-scale GWAS datasets 179 assess relationship BC across different molecular subtypes. TSMR was employed explore causal relationships, while BMA-MR method carried out validate results. assessed heterogeneity horizontal pleiotropy through Cochran's Q, MR-Egger intercept tests, MR-PRESSO. Moreover, a leave-one-out sensitivity analysis performed evaluate impact individual single nucleotide polymorphisms on MR study. Results By examining lipidome traits as exposures outcome, revealed significant effects glycerophospholipids, sphingolipids, glycerolipids risk. Specifically, for estrogen receptor-positive (ER + BC), phosphatidylcholine ( P < 0.05) phosphatidylinositol (OR: 0.916–0.966, within glycerophospholipids play roles, along with importance (diacylglycerol (OR = 0.923, 0.001) triacylglycerol, OR: 0.894–0.960, 0.05)). However, did not observe noteworthy sphingolipids ER BC. In case receptor-negative − only 1.085, 0.008), 0.909, 0.002) exerted an influence, but protective effect sterols 1.034–1.056, also discovered. prominence minimal in ER-BC. Phosphatidylethanolamine 1.091–1.119, important Conclusions findings reveal that triglycerides levels decreased BC, indicating potential role these lipid molecules. elucidates BC's intricate metabolic pathways, highlighting diverse structural variations may have varying
Language: Английский
Citations
10
BMC Bioinformatics, Journal Year: 2024, Volume and Issue: 25(1)
Published: Jan. 22, 2024
Abstract Breast cancer remains a major public health challenge worldwide. The identification of accurate biomarkers is critical for the early detection and effective treatment breast cancer. This study utilizes an integrative machine learning approach to analyze gene expression data superior biomarker drug target discovery. Gene datasets, obtained from GEO database, were merged post-preprocessing. From dataset, differential analysis between normal samples revealed 164 differentially expressed genes. Meanwhile, separate dataset 350 Additionally, BGWO_SA_Ens algorithm, integrating binary grey wolf optimization simulated annealing with ensemble classifier, was employed on datasets identify predictive genes including TOP2A, AKR1C3, EZH2, MMP1, EDNRB, S100B, SPP1. over 10,000 genes, identified 1404 in (F1 score: 0.981, PR-AUC: 0.998, ROC-AUC: 0.995) 1710 GSE45827 0.965, 0.986, 0.972). intersection DEGs selected 35 that consistently significant across methods. Enrichment analyses uncovered involvement these key pathways such as AMPK, Adipocytokine, PPAR signaling. Protein-protein interaction network highlighted subnetworks central nodes. Finally, drug-gene investigation connections anticancer drugs. Collectively, workflow robust signature cancer, illuminated their biological roles, interactions therapeutic associations, underscored potential computational approaches discovery precision oncology.
Language: Английский
Citations
9
Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)
Published: Jan. 7, 2025
Abstract Background Osimertinib has emerged as a critical element in the treatment landscape following recent clinical trials. Further investigation into mechanisms driving resistance to is necessary address restricted options and survival advantages that are compromised by patients with EGFR-mutated lung adenocarcinoma (LUAD). Methods Spatial transcriptomic proteomic analyses were utilized investigate of resistance. Co-IP, MS, RNA-seq, ChIP-seq, RIP-seq, ATAC-seq performed cell lines further explore mechanism. To validate findings, vitro vivo molecular experiments conducted. Results We found ARID1A deficiency results hindering programmed death through EZH2/PTEN/E2F1 axis. This altered axis influences PD-L1 transcription E2F1-mediated promoter activation translation via MDM2/eIF5B/PD-L1 Subsequently, increased expression eIF5B Importin-β1, promoting nuclear-translocation. The nuclear (nPD-L1) interacts CD44, leading nPD-L1 complex formation, RASGEF1A promoter, initiation Ras pathway, contributing Targeting transcription, nuclear-translocation using lipid nanoparticles (LNPs) overcomes deficiency-induced Conclusion promotes translocation induces
Language: Английский
Citations
1
Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)
Published: Feb. 19, 2025
Abstract Background Brain metastasis (BrM) poses a significant challenge to the prognosis and quality of life for patients with non-small cell lung cancer (NSCLC). Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in central nervous system (CNS), has been implicated progression various tumors. However, its potential role BrM NSCLC underlying mechanisms remain largely unexplored. Methods A multi-omics approach combined vivo vitro experiments identified GABA as key target NSCLC. Functional mechanistic studies were conducted investigate how mediates brain through activation NF-κB pathway. Results levels significantly elevated both cells serum who had BrM. markedly enhanced metastatic capabilities malignancy cells. Mechanistically, tumor tendency can inhibit 4-aminobutyrate aminotransferase (ABAT) by downregulating forkhead box A2 (FOXA2) expression, leading increased accumulation. subsequently activates pathway astrocytes, thus facilitating Conclusions Our findings indicate that plays crucial development activating FOXA2/ABAT/GABA axis. Additionally, interaction between astrocytes creates microenvironment promotes colonization.
Language: Английский
Citations
1
BMC Genomics, Journal Year: 2025, Volume and Issue: 26(1)
Published: Feb. 24, 2025
Different chicken breeds exhibit distinct muscle phenotypes resulting from selective breeding, but little is known about the molecular mechanisms responsible for this phenotypic difference. Skeletal composed of a large number heterogeneous cell populations. Differences in differentiation and interaction populations play key role difference skeletal phenotype. In current study, we performed single-cell RNA sequencing (scRNA-seq) on leg Daheng broiler (DH, cultivated breed) Tibetan (TC, native at embryonic (E) 10, E14 E18. A comprehensive atlas muscle, consisting 29,579 high-quality cells representing 6 types was built. The trajectory Myoblasts fibro-adipogenic progenitors (FAPs) constructed through pseudotemporal analysis. Our results revealed different developmental trajectories dynamic gene expression profiles 3 subtypes myoblasts 5 FAPs two breeds. showed earlier myogenesis less compared with broiler. By comparing switch status time genes breeds, SNRPG,SNRPE,EIF4EBP1 HSP90AB1 were considered as potentially critical myogenesis, MYOG,MYBPH,APOA1, MGP played dominant roles adipogenesis. Intercellular networks that strong complex intercellular communication contained during growth development. These findings differences development between TC DH chickens. data provide better understanding valuable information genetic breeding chicken.
Language: Английский
Citations
1
International Journal of Oncology, Journal Year: 2024, Volume and Issue: 65(4)
Published: Aug. 30, 2024
The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis local recurrence. immune microenvironment (TME) consists cells, cytokines immunomodulators, collectively they influence the response treatment. Epigenetic changes including DNA methylation histone modification, as well increased exportation have been reported contribute development in cancers. In past few years, majority studies on tumors only focused progression from mechanistic standpoint; examined whether TME can also affect growth resistance. Recently, emerging evidence raised more concerns regarding role present review, it was discussed how suppressive adapts characterized by cooperation cytokines, stromal cells extracellular matrix. Furthermore, reviewed these immunological or metabolic alter immuno‑surveillance thus facilitate addition, potential targets developing novel therapeutic strategies improve individualized therapy treatment were revealed.
Language: Английский
Citations
6
iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109902 - 109902
Published: May 3, 2024
Highlights•m6A reader YTHDF2 was highly expressed in pro-tumoral macrophages•YTHDF2 correlates with and immuno-suppressing signals of macrophages•Identification SPI1 as key transcriptional regulator YTHDF2-high macrophage•Ythdf2 associates phenotype polarization macrophages the miceSummaryPatients triple-negative breast cancer (TNBC) frequently experience resistance to chemotherapy, leading recurrence. The approach optimizing anti-tumoral immunological effect is promising overcoming such resistance, given heterogeneity lack biomarkers TNBC. In this study, we focused on YTHDF2, an N6-methyladenosine (m6A) RNA-reader protein, macrophages, one most abundant intra-tumoral immune cells. Using single-cell sequencing ex vivo experiments, discovered that significantly promotes closely associated down-regulated antigen-presentation signaling other cells vitro deprivation favors effect. Expressions multiple transcription factors, especially SPI1, were consistently observed providing potential therapeutic targets for new strategies. conclusion, appears promote effects while suppressing activity, indicating treatment targeting or its factors could be a strategy chemoresistant TNBC.Graphical abstract
Language: Английский
Citations
5
Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)
Published: April 7, 2024
Abstract Background Fatty acids synthesis and metabolism (FASM)-driven lipid mobilization is essential for energy production during nutrient shortages. However, the molecular characteristics, physiological function clinical prognosis value of FASM-associated gene signatures in hepatocellular carcinoma (HCC) remain elusive. Methods The Gene Expression Omnibus database (GEO), Cancer Genome Atlas (TCGA), International Consortium (ICGC) were utilized to acquire transcriptome data information HCC patients. ConsensusClusterPlus was employed unsupervised clustering. Subsequently, immune cell infiltration, stemness index therapeutic response among distinct clusters decoded. tumor dysfunction exclusion (TIDE) algorithm anticipate patients towards immunotherapy, genomics drug sensitivity cancer (GDSC) tool predict their antineoplastic medications. Least absolute shrinkage selection operator (LASSO) regression analysis protein–protein interaction (PPI) network construct prognostic model identity hub gene. Single RNA sequencing (scRNA-seq) CellChat used analyze cellular interactions. FASM effect on promoting progression confirmed through a series functional experiments. Results Twenty-six FASM-related genes showed differential expression HCC. Based these genes, two subtypes established, including Cluster1 Cluster2 subtype. Compared with cluster2, subtype exhibited worse prognosis, higher risk, immunosuppressive cells infiltrations, escape, enhanced treatment-resistant. PPI identified Acetyl-CoA carboxylase1 (ACACA) as central predicted poor prognosis. A strong between stem (CSCs) high ACACA macrophages CD74 molecule (CD74) integrin subunit beta 1 (ITGB1) signaling identified. Finally, increased observed patients, whereas depleted inhibited straits resistance cells. Conclusions This study provides resource understanding heterogeneity Evaluating patterns can help provide new insights into treatment
Language: Английский
Citations
4