Molecular Immunology, Journal Year: 2025, Volume and Issue: 180, P. 86 - 95
Published: Feb. 28, 2025
Language: Английский
Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 77, P. 101126 - 101126
Published: Aug. 6, 2024
Language: Английский
Citations
23
Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(11)
Published: June 29, 2024
Abstract Distant metastasis remains the primary cause of morbidity in patients with breast cancer. Hence, development more efficacious strategies and exploration potential targets for metastatic cancer are urgently needed. The data six brain metastases (BCBrM) from two centres were collected, a comprehensive landscape entire tumour ecosystem was generated through utilisation single‐cell RNA sequencing. We utilised Monocle2 CellChat algorithms to investigate interrelationships among each subcluster. In addition, multiple signatures collected evaluate key components subclusters multi‐omics methodologies. Finally, we elucidated common expression programs malignant cells, experiments conducted vitro vivo determine functions interleukin enhancer‐binding factor 2 ( ILF2 ), which is gene module, BCBrM progression. found that major cell type exhibited diverse characteristics. Besides, our study indicated specifically associated BCBrM, experimental validations further demonstrated deficiency hindered Our offers novel perspectives on heterogeneity suggests could serve as promising biomarker or therapeutic target BCBrM.
Language: Английский
Citations
12
Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(2)
Published: Feb. 1, 2024
Targeted therapy for triple-negative breast cancer (TNBC) remains a challenge. N6-methyladenosine (m
Language: Английский
Citations
11
Cancer Letters, Journal Year: 2024, Volume and Issue: 592, P. 216907 - 216907
Published: April 27, 2024
Language: Английский
Citations
10
Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(7)
Published: March 20, 2024
Abstract Circular RNAs (circRNAs) function as tumour promoters or suppressors in bladder cancer (BLCA) by regulating genes involved macrophage recruitment and polarization. However, the underlying mechanisms are largely unknown. The aim of this study was to determine biological role circLOC729852 BLCA. CircLOC729852 upregulated BLCA tissues correlated with increased proliferation, migration epithelial mesenchymal transition (EMT) BCLA cells. MiR‐769‐5p identified a target for circLOC729852, which can upregulate IL‐10 expression directly binding suppressing miR‐769‐5p. Furthermore, our results indicated that circLOC729852/miR‐769‐5p/IL‐10 axis modulates autophagy signalling cells promotes M2 polarization TAMs activating JAK2/STAT3 pathway. In addition, also promoted growth xenografts infiltration vivo. Thus, functions an oncogene inducing secretion TAMs, then facilitates cell migration. Taken together, is potential diagnostic biomarker therapeutic
Language: Английский
Citations
9
Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)
Published: Feb. 6, 2025
Abstract Background D-2-hydroxyglutarate (D-2HG), an oncometabolite derived from the tricarboxylic acid cycle. Previous studies have reported diverse effects of D-2HG in pathophysiological processes, yet its role breast cancer remains largely unexplored. Methods We applied advanced biosensor approach to detect levels samples. then investigated biological functions through multiple vitro and vivo assays. A joint MeRIP-seq RNA-seq strategy was used identify target genes regulated by D-2HG-mediated N6-methyladenosine (m 6 A) modification. RNA pull-down assays were further reader that could specifically recognize m modification on angiopoietin like 4 (ANGPTL4) mRNA immunoprecipitation confirm findings. Results found accumulated triple-negative (TNBC), exerting oncogenic both promoting TNBC cell growth metastasis. Mechanistically, enhanced global modifications cells, notably upregulating ANGPTL4 mRNA, which mediated inhibition Fat-mass obesity-associated protein (FTO), resulting increased recognition A-modified YTH binding F1 (YTHDF1), thereby translation ANGPTL4. As a secretory protein, subsequently activated integrin-mediated JAK2/STAT3 signaling cascade cells autocrine signaling. Notably, knockdown or treatment with GLPG1087 (an integrin antagonist) significantly reduced D-2HG-induced proliferation metastasis cells. Additionally, promote macrophage M2 polarization within tumor microenvironment via paracrine signaling, driving progression. The association poor prognosis patients underscores clinical relevance. Conclusions Our study unveils previously unrecognized for progression targeting D-2HG/FTO/m A/ANGPTL4/integrin axis can serve as promising therapeutic patients.
Language: Английский
Citations
1
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
1
Cellular Signalling, Journal Year: 2024, Volume and Issue: 117, P. 111079 - 111079
Published: Feb. 8, 2024
Language: Английский
Citations
7
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: June 8, 2024
Abstract Background Breast cancer is the most common malignant tumor, and metastasis remains major cause of poor prognosis. Glucose metabolic reprogramming one prominent hallmarks in cancer, providing nutrients energy to support dramatically elevated tumor growth metastasis. Nevertheless, potential mechanistic links between glycolysis breast progression have not been thoroughly elucidated. Methods RNA-seq analysis was used identify glucose metabolism-related circRNAs. The expression circSIPA1L3 tissues serum examined by qRT-PCR, further assessed its diagnostic value. We also evaluated prognostic analyzing a cohort 238 patients. Gain- loss-of-function experiments, transcriptomic analysis, molecular biology experiments were conducted explore biological function regulatory mechanism circSIPA1L3. Results Using identified as critical mediator responsible for adaption upon stress. revealed that exerted stimulative effect on glycolysis, which could be transported exosomes facilitated behaviors among cells. Significantly, lactate secretion caused circSIPA1L3-mediated enhancement promoted recruitment associated macrophage their tumor-promoting roles. Mechanistically, EIF4A3 induced cyclization cytoplasmic export circSIPA1L3, inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing UPS7-IGF2BP3 interaction. Furthermore, increased mRNA stability carrier SLC16A1 intake enhancer RAB11A either strengthening interaction with or sponging miR-665, leading enhanced glycolytic metabolism. Clinically, indicated unfavorable prognosis base Moreover, highly expressed patients exhibited high value Conclusions Our study highlights oncogenic role mediating metabolism, might serve promising biomarker therapeutic target cancer.
Language: Английский
Citations
7
Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14
Published: April 18, 2024
Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its propensity for metastasis and poor prognosis. TNBC evades the body's immune system recognition attack through various mechanisms, including Janus Kinase 2 (JAK2)/signal transducer activator of transcription 3 (STAT3) signaling pathway. This pathway, characterized by heightened activity in numerous solid tumors, exhibits pronounced activation specific subtypes. Consequently, targeting JAK2/STAT3 pathway emerges as promising precise therapeutic strategy TNBC. The signal transduction cascade predominantly involves receptor tyrosine kinases, kinase JAK2, factor STAT3. Ongoing preclinical studies research are actively investigating this potential target treatment. article comprehensively reviews investigations into treatment using small molecule compounds. review explores role therapeutics, evaluating benefits limitations active inhibitors proteolysis-targeting chimeras aim is facilitate development novel small-molecule compounds that effectively. Ultimately, work seeks contribute enhancing efficacy patients with
Language: Английский
Citations
6