Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 7, 2025

Kidney renal clear cell carcinoma (KIRC), a therapy-resistant aggressive kidney cancer, exhibits resistance to immune checkpoint inhibitors. Altered sialylation is involved in tumor development, affecting microenvironment dynamics. In the study, through systematic bioinformatics analysis and experimental verification, we demonstrated that ST3Gal5 expression was elevated tissues of KIRC patients, correlating with poor prognosis, ST3Gal1 downregulated associated better prognosis. Immunohistochemistry confirmed patterns 30 patients. Furthermore, patients were stratified into two clusters based on levels using consensus clustering investigate their roles tumorigenesis, characteristics treatment sensitivity. Cluster 2, characterized by increased expression, exhibited checkpoints, infiltration, escape scores, worse Knockdown lines (786-O 769-P) resulted reduced proliferation, migration, invasion vivo vitro. Together, dysregulation sialyltransferases (ST3Gal1 ST3Gal5) influences tumorigenesis responses. These findings underscore potential as prognostic factors immunotherapy targets for KIRC.

Language: Английский

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Molecular mechanisms and clinical significance of perineural invasion in malignancies: the pivotal role of tumor-associated Schwann cells in cancer progression and metastasis

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(5)

Published: April 21, 2025

Language: Английский

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Implications of Mucin-Type O-Glycosylation in Alzheimer’s Disease

Molecules, Journal Year: 2025, Volume and Issue: 30(9), P. 1895 - 1895

Published: April 24, 2025

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders linked to aging. Major hallmarks AD pathogenesis include amyloid-β peptide (Aβ) plaques, which are extracellular deposits originating from processing amyloid precursor protein (APP), and neurofibrillary tangles (NFTs), intracellular aggregates tau protein. Recent evidence indicates that disruptions in metal homeostasis impaired immune recognition these trigger neuroinflammation, ultimately driving progression. Therefore, a more comprehensive approach needed understand underlying causes disease. Patients with present abnormal glycan profiles, known AD-related molecules either modified glycans or involved regulation. A deeper understanding how O-glycosylation influences balance between amyloid-beta production clearance, as well microglia’s pro- anti-inflammatory responses, crucial for deciphering early pathogenic events AD. This review aims provide summary extensive research conducted on role mucin-type AD, discussing its onset recognition.

Language: Английский

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Synthesis and Thermodynamic Evaluation of Sialyl‐Tn MUC1 Glycopeptides Binding to Macrophage Galactose‐Type Lectin

ChemBioChem, Journal Year: 2024, Volume and Issue: unknown

Published: June 15, 2024

Abstract Interactions between the tumor‐associated carbohydrate antigens of Mucin 1 (MUC1) and carbohydrate‐binding proteins, lectins, often lead to creation a pro‐tumor microenvironment favoring tumor initiation, progression, metastasis, immune evasion. Macrophage galactose binding lectin (MGL) is C‐type receptor found on antigen‐presenting cells that facilitates uptake for antigen presentation, modulating response homeostasis, autoimmunity, cancer. Considering crucial role forms MUC1 MGL in immunology, thorough understanding their interaction essential it be exploited cancer vaccine strategies. The synthesis glycopeptide models carrying single or multiple Tn and/or sialyl‐Tn antigen(s) described. A novel approach threonine building block suitable solid phase peptide was developed. thermodynamic profile human analyzed using isothermal titration calorimetry. measured dissociation constants sialyl‐Tn‐bearing epitopes were consistently lower compared ranged from 10 μM mono‐ triglycosylated peptide, respectively. All studied interactions, regardless glycan's site attachment density, exhibited enthalpy‐driven thermodynamics.

Language: Английский

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Mechanistic and Therapeutic Implications of Protein and Lipid Sialylation in Human Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11962 - 11962

Published: Nov. 7, 2024

Glycan structures of glycoproteins and glycolipids on the surface glycocalyx luminal sugar layers intracellular membrane compartments in human cells constitute a key interface between biological processes external environments. Sialic acids, class alpha-keto acid sugars with nine-carbon backbone, are frequently found as terminal residues these glycoconjugates, forming critical components layers. Changes status content cellular sialic acids closely linked to many diseases such cancer, cardiovascular, neurological, inflammatory, infectious, lysosomal storage diseases. The molecular machineries responsible for biosynthesis sialylated glycans, along their interacting partners, important therapeutic strategies targets drug development. purpose this article is comprehensively review recent literature provide new scientific insights into mechanisms implications sialylation across various Recent advances clinical developments acid-related therapies also summarized discussed.

Language: Английский

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