SIRPB1 regulates inflammatory factor expression in the glioma microenvironment via SYK: functional and bioinformatics insights

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 9, 2024

Abstract Background SIRPB1 expression is upregulated in various tumor types, including gliomas, and known to contribute progression; nevertheless, its function the immune milieu of gliomas still mainly unknown. Methods This study, we analyzed 1152 normal samples from GTEx database 670 glioma TCGA investigate relationship between clinicopathological features. Moreover, gene knockout THP-1 cell lines were constructed using CRISPR/Cas9 induced into a co-culture macrophages cells vitro learn more about role milieu. Lastly, established prognostic model predict effect on prognosis. Results Significantly higher levels found which had an adverse correlated poorly with patient survival. activation certain antibodies results SYK phosphorylation subsequent calcium, MAPK, NF-κB signaling pathways. phenomenon primarily observed myeloid-derived as opposed cells. In demonstrated that showed decreased IL1RA, CCL2, IL-8, recovered upon ectopic but reduced again following treatment inhibitor GS9973. Critically, lower overall survival rate was linked increased expression. Making use along additional variables, nomogram high degree prediction accuracy. Conclusions Our study demonstrates can be activated by via SIRPB1, subsequently reprogramming TME, suggesting could serve promising therapeutic target for gliomas.

Language: Английский

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Targeting drug‐tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Aug. 24, 2023

Drug resistance remains the greatest challenge in improving outcomes for cancer patients who receive chemotherapy and targeted therapy. Surmounting evidence suggests that a subpopulation of cells could escape intense selective drug treatment by entering drug-tolerant state without genetic variations. These (DTCs) are characterized with slow proliferation rate reversible phenotype. They reside tumor region may serve as reservoir resistant phenotypes. The survival DTCs is regulated epigenetic modifications, transcriptional regulation, mRNA translation remodeling, metabolic changes, antiapoptosis, interactions microenvironment, activation signaling pathways. Thus, targeting regulators opens new avenue therapy-resistant tumors. In this review, we first provide an overview common characteristics regulating networks development. We also discuss potential therapeutic opportunities to target DTCs. Last, current challenges prospects DTC-targeting approach overcome acquired resistance. Reviewing latest developments DTC research be essential discovering methods eliminate DTCs, which represent novel strategy preventing future.

Language: Английский

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Periplogenin inhibits pathologic synovial proliferation and infiltration in rheumatoid arthritis by regulating the JAK2/3-STAT3 pathway

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 128, P. 111487 - 111487

Published: Jan. 5, 2024

Language: Английский

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Targeting tumorous Circ-E-Cadherinencoded C-E-Cad inhibits the recruitment and function of breast cancer-associated myeloid-derived suppressor cells

Pharmacological Research, Journal Year: 2024, Volume and Issue: 204, P. 107204 - 107204

Published: May 2, 2024

We previously demonstrated that the C-E-cad protein encoded by circ-E-cadherin promotes self-renewal of glioma stem cells. The expression pattern in breast cancer and its potential function tumor microenvironment are unclear. was detected specimens. influence on MDSCs assessed using FACS vivo tumorigenesis experiments. synergistic effect anti-C-E-cad anti-PD-1 antibodies validated vivo. were found to be upregulated vs. normal samples. recruitment MDSCs, especially PMN-MDSCs. activates EGFR signaling cells transcription CXCL8; moreover, binds maintains glycolysis Targeting enhanced efficiency. Our data suggested is markedly overexpressed MDSC survival. increases efficacy immune checkpoint inhibitor therapy.

Language: Английский

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Deep dissection of stemness-related hierarchies in hepatocellular carcinoma

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 16, 2023

Increasing evidence suggests that hepatocellular carcinoma (HCC) stem cells (LCSCs) play an essential part in HCC recurrence, metastasis, and chemotherapy radiotherapy resistance. Multiple studies have demonstrated stemness-related genes facilitate the progression of tumors. However, mechanism by which contribute to is not well understood. Here, we aim construct a score (SRscores) model for deeper analysis genes, assisting with prognosis individualized treatment patients.Further, found gene LPCAT1 was highly expressed tumor tissues immunohistochemistry, sphere-forming assay revealed knockdown inhibited ability cells.We used TCGA-LIHC dataset screen from MSigDB database. Prognosis, microenvironment, immunological checkpoints, immune dysfunction, rejection, sensitivity, putative biological pathways were examined. Random forest created SRscores model. The anti-PD-1/anti-CTLA4 immunotherapy, mutational burden, medication cancer cell index compared between high- low-risk groups. We also examined risk scores different types using single-cell RNA sequencing data correlated transcription factor activity genes. Finally, tested core marker expression functions.Patients can be divided into two subtypes (Cluster1 Cluster2) based on dataset's identification 11 Additionally, developed subtypes. Cluster2 group lowest had superior survival immunotherapy response than Cluster1 highest SRscores. high significantly more enriched classical low factors are correlated. rat liver promotes sphere formation.A utilized predict patients as their immunotherapy.

Language: Английский

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Enhanced Antitumor Activity of Korean Black Soybean Cultivar ‘Soman’ by Targeting STAT-Mediated Aerobic Glycolysis

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 228 - 228

Published: Feb. 18, 2025

Black soybeans have numerous health benefits owing to their high polyphenolic content, antioxidant activity, and antitumor effects. We previously reported that the Korean black soybean cultivar 'Soman' possesses higher anthocyanin isoflavone contents superior potential than other cultivars landraces (Seoritae) do. Here, we investigated compared effects of Soman Seoritae aimed elucidate possible mechanisms action. inhibited cancer cell proliferation was more potent Seoritae. Mechanistically, phosphorylation signal transducer activator transcription (STAT1, 3, 5) in a reactive oxygen species (ROS)-independent manner, subsequently decreasing glycolytic enzyme expression activities pyruvate kinase lactate dehydrogenase. Thus, suppressed glucose uptake, production, ATP production cells. Additionally, it tumor growth B16F10 murine melanoma syngeneic model, accompanied by reduced STAT1 decreased Soman-treated mice, potently observed Seoritae-treated mice. These findings showed exerted suppressing STAT-mediated aerobic glycolysis proliferation. Overall, our demonstrate potent, tumor-suppressive role human uncover novel molecular mechanism for its therapeutic treatment.

Language: Английский

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STAT3 Signaling Pathway in Health and Disease

MedComm, Journal Year: 2025, Volume and Issue: 6(4)

Published: March 30, 2025

ABSTRACT Signal transducer and activator of transcription 3 (STAT3) is a critical factor involved in multiple physiological pathological processes. While STAT3 plays an essential role homeostasis, its persistent activation has been implicated the pathogenesis various diseases, particularly cancer, bone‐related autoimmune disorders, inflammatory cardiovascular neurodegenerative conditions. The interleukin‐6/Janus kinase (JAK)/STAT3 signaling axis central to activation, influencing tumor microenvironment remodeling, angiogenesis, immune evasion, therapy resistance. Despite extensive research, precise mechanisms underlying dysregulated disease progression remain incompletely understood, no United States Food Drug Administration (USFDA)‐approved direct inhibitors currently exist. This review provides comprehensive evaluation STAT3's health disease, emphasizing involvement cancer stem cell maintenance, metastasis, inflammation, drug We systematically discuss therapeutic strategies, including JAK (tofacitinib, ruxolitinib), Src Homology 2 domain (S3I‐201, STATTIC), antisense oligonucleotides (AZD9150), nanomedicine‐based delivery systems, which enhance specificity bioavailability while reducing toxicity. By integrating molecular mechanisms, pathology, emerging interventions, this fills knowledge gap STAT3‐targeted therapy. Our insights into crosstalk, epigenetic regulation, resistance offer foundation for developing next‐generation with greater clinical efficacy translational potential.

Language: Английский

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Loss of macrophage fibroblast growth factor 12 attenuates cardiac fibrosis in pressure-overloaded myocardium

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 154, P. 114614 - 114614

Published: April 7, 2025

Language: Английский

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Przewaquinone A, as a natural STAT3 inhibitor, suppresses the growth of melanoma cells and induces autophagy

Phytomedicine, Journal Year: 2025, Volume and Issue: 142, P. 156810 - 156810

Published: April 26, 2025

Language: Английский

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Association of STAT6 gene polymorphism with atopic asthma among Yemeni children in Sana’a city, Yemen

BMC Pediatrics, Journal Year: 2025, Volume and Issue: 25(1)

Published: May 15, 2025

Language: Английский

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