Heliyon, Journal Year: 2024, Volume and Issue: unknown, P. e37402 - e37402
Published: Sept. 1, 2024
Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(2), P. e010787 - e010787
Published: Feb. 1, 2025
Background Lung adenocarcinoma (LUAD) presents significant challenges in prognosis and treatment efficacy evaluation. While post-translational modifications are known to influence tumor progression, their prognostic value LUAD remains largely unexplored. Methods We developed a modification learning signature (PTMLS) using machine techniques, analyzing data from 1231 patients across seven global cohorts. The signature’s predicting immunotherapy response was evaluated 12 cohorts spanning multiple cancer types (n=1201). An in-house tissue cohort (n=171) used validate beta-1,4-galactosyltransferase 2’s (B4GALT2’s) significance. role of B4GALT2 immune exclusion investigated through vivo vitro experiments. Results established PTMLS exhibited exceptional predictive capabilities patient outcomes, surpassing the 98 existing indicators. system’s validated diverse malignancy categories for immunotherapeutic assessment. From biological perspective, correlations were observed between immunological parameters, whereby elevated levels characterized by attenuated responses immunologically cold neoplastic features. Within framework, identified as crucial molecular component (r=0.82, p<0.05), its heightened expression linked unfavorable clinical outcomes cases, particularly specimens exhibiting CD8-depleted phenotypes. spatial distribution patterns cell populations, specifically CD8+ T lymphocytes CD20+ B lymphocytes, elucidated multiplexed immunofluorescence analysis. Laboratory investigations subsequently B4GALT2’s regulatory on cellular expansion both laboratory cultures animal models. Significantly, suppression found enhance lymphocyte populations functional status, thereby potentiating anti-programmed death protein 1 studies. This phenomenon reduced CD62L+CD8 alongside GZMB+/CD44+/CD69+CD8 populations. Conclusion system represents an effective instrument individualized evaluation stratification identification previously unrecognized oncogenic factor involved novel therapeutic avenue optimization.
Language: Английский
Citations
9
Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15
Published: July 30, 2024
The P2X7 receptor (P2X7R), an ATP-gated ion channel, has emerged as a crucial player in neuroinflammation and promising therapeutic target for neurodegenerative disorders. This review explores the current understanding of P2X7R's structure, activation, physiological roles, focusing on its expression function microglial cells. article examines receptor's involvement calcium signaling, polarization, well role pathogenesis Alzheimer's disease, Parkinson's multiple sclerosis, amyotrophic lateral sclerosis. highlights complex nature P2X7R discussing potential neuroprotective neurotoxic effects depending disease stage context. It also addresses development antagonists their progress clinical trials, identifying key research gaps future perspectives P2X7R-targeted therapy development. By providing comprehensive overview state knowledge directions, this serves valuable resource researchers clinicians interested exploring targeting treatment
Language: Английский
Citations
9
Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156673 - 156673
Published: March 1, 2025
Language: Английский
Citations
1
Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 394 - 394
Published: Feb. 25, 2024
Glycoproteomics has accelerated in recent decades owing to numerous innovations the analytical workflow. In particular, new mass spectrometry strategies have contributed inroads O-glycoproteomics, a field that lags behind N-glycoproteomics due several unique challenges associated with complexity of O-glycosylation. This review will focus on progress sample preparation, enrichment strategies, and MS/MS techniques for identification characterization O-glycoproteins.
Language: Английский
Citations
6
Genes, Journal Year: 2024, Volume and Issue: 15(6), P. 777 - 777
Published: June 13, 2024
Members of the SOX (SRY-related HMG box) family transcription factors are crucial for embryonic development and cell fate determination. This review investigates role SOX3 in cancer, as aberrations expression have been implicated several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, leukemia. These dysregulations modulate key cancer outcomes such apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cycle, proliferation, contributing to development. exhibits varied patterns correlated with clinicopathological parameters diverse tumor types. aims elucidate nuanced tumorigenesis, correlating its clinical pathological characteristics patients cellular modelsBy providing a comprehensive exploration involvement this underscores multifaceted across distinct The complexity uncovered function emphasizes need further research unravel full potential therapeutics.
Language: Английский
Citations
4
Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 265, P. 108749 - 108749
Published: Nov. 16, 2024
Language: Английский
Citations
4
Advanced Science, Journal Year: 2024, Volume and Issue: 11(29)
Published: June 14, 2024
Abstract Immunosuppression is a major hallmark of tumor progression in non‐small cell lung cancer (NSCLC). Cluster differentiation 147 (CD147), an important pro‐tumorigenic factor, closely linked to NSCLC immunosuppression. However, the role CD147 di‐methylation immunosuppressive microenvironment (TME) remains unclear. Here, at Lys148 (CD147‐K148me2) identified as common post‐translational modification (PTM) that significantly associated with unsatisfying survival outcomes among sufferers, especially those advanced stages disease. The methyltransferase NSD2 catalyzes generate CD147‐K148me2. Further analysis demonstrates CD147‐K148me2 reestablishes TME and promotes progression. Mechanistically, this interaction between cyclophilin A (CyPA) CD147, turn, increases CCL5 gene transcription by activating p38‐ZBTB32 signaling, leading increased cell‐derived secretion. Subsequently, CD147‐K148me2‐mediated upregulation facilitates M2‐like tumor‐associated macrophage (TAM) infiltration tissues via CCL5/CCR5 axis‐dependent intercellular crosstalk cells macrophages, which inhibited blocking targeted antibody 12C8. Overall, study reveals CD147‐K148me2‐driven development immunosuppression, provides potential interventional strategy for PTM‐targeted therapy.
Language: Английский
Citations
3
Cancer and Metastasis Reviews, Journal Year: 2025, Volume and Issue: 44(1)
Published: Jan. 17, 2025
Abstract Cancer stem cells play an important role in tumor progression and chemotherapy resistance. Leucine-rich G repeat-containing protein-coupled receptor 5 (LGR5) has been identified as a cancer cell marker several types. LGR5 is involved development via pathways including WNT/β-catenin signaling pathway. plays by promoting migration, invasion, metastasis, angiogenesis many cancers colorectal, brain, gastric, ovarian cancer. This review summarises the current knowledge on expression functional of cancers, molecular mechanisms regulated LGR5, relationship between The also includes highlights potential strategies to inhibit function. majority studies have shown that progression, metastasis resistance however, some contexts can activate tumor-suppressive negative promote progression. targeting promising anti-cancer treatment but effect complex may be dependent type, microenvironment cross-talk with other molecules
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1066 - 1066
Published: Jan. 26, 2025
Protein phosphorylation is a dynamic and reversible modification involved in almost all cellular processes. Numerous investigations have shown that protein enzymes (PPMEs) regulate play an important role the occurrence treatment of tumors. However, there still lack effective insights into value PPMEs classification patients with lung adenocarcinoma (LUAD). Here, four topological algorithms identified 15 hub from protein–protein interaction (PPI) network. This PPI network was constructed using 124 significantly correlated 35 cancer hallmark-related pathways. Our study illustrates these can affect survival LUAD form somatic mutation or expression perturbation. Consistency clustering based on recognized two subtypes (namely cluster1 cluster2) LUAD. Compared cluster1, prognosis cluster2 worse. disparity probably attributed to higher tumor burden, male proportion, more significant disturbance cluster2. Moreover, also different characteristics terms immune activity, infiltration level, immunotherapy response, drug sensitivity. We PSig scoring system by principal component analysis algorithm estimate level individual patients. Patients high low score groups demonstrated rate, gene cell abundance, sensitivity treatment. work reveals plays non-negligible microenvironment Evaluating status contribute enhancing our cognition guiding formulation personalized strategies.
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: Jan. 29, 2025
Succinylation represents an emerging class of post-translational modifications (PTMs), characterized by the enzymatic or non-enzymatic transfer a negatively charged four-carbon succinyl group to ϵ-amino lysine residues, mediated succinyl-coenzyme A. Recent studies have highlighted involvement succinylation in various diseases, particularly cancer progression. Sirtuin 5 (SIRT5), member sirtuin family, has been extensively studied for its robust desuccinylase activity, alongside deacetylase function. To date, only limited number SIRT5 substrates identified. These mediate diverse physiological processes such as glucose oxidation, fatty acid ammonia detoxification, reactive oxygen species scavenging, anti-apoptosis, and inflammatory responses. The regulation these activities can occur through either same activity acting on different distinct targeting substrate. Aberrant expression closely linked tumorigenesis disease progression; however, role remains controversial. exhibits dual functionalities: it promote tumor proliferation, metastasis, drug resistance, metabolic reprogramming, thereby oncogene; conversely, also inhibit cell growth induce apoptosis, functioning suppressor gene. This review aims provide comprehensive overview current research status SIRT5. We discuss structural characteristics regulatory mechanisms, compare functions with other family members, elucidate mechanisms regulating activity. Specifically, we focus modification progression, highlighting how desuccinylation modulates development delineating underlying involved.
Language: Английский
Citations
0