Cross-disease transcriptomic analysis reveals DOK3 and PAPOLA as therapeutic targets for neuroinflammatory and tumorigenic processes DOI Creative Commons
Xingqiao Wang,

Yusong Bian,

Wei-Guang Chen

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Дек. 12, 2024

Objective Subarachnoid hemorrhage (SAH) and tumorigenesis share numerous biological complexities; nevertheless, the specific gene expression profiles underlying mechanisms remain poorly understood. This study aims to identify differentially expressed genes (DEGs) that could serve as biomarkers for diagnosis prognosis. Methods Gene datasets (GSE122063, GSE13353, GSE161870) were analyzed using machine learning algorithms logistic regression DEGs associated with both SAH tumorigenesis. Lasso receiver operating characteristic (ROC) curve analysis employed evaluate classification accuracy of these genes. Validation critical was performed through pan-cancer experimental studies, focusing on role DOK3 in modulating inflammation oxidative stress U251MG glioblastoma BV2 microglia cells. Results Fifteen common identified, PAPOLA highlighted crucial implicated neurodegenerative processes. Experimental validation demonstrated overexpression significantly reduced pro-inflammatory cytokine levels markers while enhancing antioxidant enzyme activity. Additionally, influenced tumorigenic processes such apoptosis, cell cycle regulation, proliferation, effectively mitigating LPS-induced cytotoxicity microglial Conclusions play roles related neurodegeneration, presenting themselves potential prognostic therapeutic targets. Notably, exhibits an antitumor agent anti-inflammatory antioxidative properties, offering benefits cancer neuroinflammatory conditions.

Язык: Английский

Unraveling the metabolic‒epigenetic nexus: a new frontier in cardiovascular disease treatment DOI Creative Commons
Jun Ouyang, Dong-de Wu,

Y. Gan

и другие.

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 18, 2025

Abstract Cardiovascular diseases are the leading causes of death worldwide. However, there still shortcomings in currently employed treatment methods for these diseases. Therefore, exploring molecular mechanisms underlying cardiovascular is an important avenue developing new strategies. Previous studies have confirmed that metabolic and epigenetic alterations often involved across patients. Moreover, factors interact with each other affect progression a coordinated manner. Lactylation novel posttranslational modification (PTM) links metabolism epigenetics affects disease progression. analyzing crosstalk between cellular expected to provide insights development The purpose this review describe relationship heart such as failure, myocardial infarction, atherosclerosis, focus on acylation methylation, propose potential therapeutic measures.

Язык: Английский

Процитировано

0

Targeting exercise-related genes and placental growth factor for therapeutic development in head and neck squamous cell carcinoma DOI Creative Commons

Qingyuan Shi,

Haiyue Ying,

Weibin Weng

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Окт. 4, 2024

Background Human cancers, including head and neck squamous cell carcinoma (HNSCC), are complex heterogeneous diseases driven by uncontrolled growth proliferation. Post-translational modifications (PTMs) of proteins play a crucial role in cancer progression, making them promising target for pharmacological intervention. This study aims to identify key exercise-related genes with prognostic value HNSCC through comprehensive bioinformatics analysis, particular focus on the therapeutic potential placental factor (PIGF). Methods Transcriptome data were obtained from The Cancer Genome Atlas (TCGA) database. Differently expressed (DEGs) identified analyzed their significance. Exercise-related gene sets retrieved Gene Set Enrichment Analysis (GSEA) Functional enrichment analyses, Ontology (GO), Kyoto Encyclopedia Genes Genomes (KEGG), GSEA, conducted. biological functions clinical implications further explored single-gene expression immune infiltration vitro cellular experiments. Results associated survival prognosis HNSCC. GO KEGG pathway analyses highlighted these genes, Kaplan-Meier curves confirmed value. PIGF analysis using TCGA showed its diagnostic potential, higher linked advanced tumor stages. Single-cell sequencing revealed PIGF’s microenvironment. In experiments demonstrated that plays pivotal enhancing proliferation colony formation HNSCC, knockdown significantly impairing functions, highlighting importance regulation. Additionally, predictive performance drug sensitivity across datasets suggests as target, offering opportunities modulate microenvironment improve outcomes treatment. Conclusion provides new insights into molecular mechanisms underlying identifies particularly PIGF, biomarkers treatment personalized medicine. By focusing PTMs our findings suggest targeting may offer innovative strategies.

Язык: Английский

Процитировано

1

Paromomycin targets HDAC1-mediated SUMOylation and IGF1R translocation in glioblastoma DOI Creative Commons
Min Zhong,

Yuejie Guo,

Ning Luo

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Дек. 11, 2024

Objective This study investigates the effects of Paromomycin on SUMOylation-related pathways in glioblastoma (GBM), specifically targeting HDAC1 inhibition. Methods Using TCGA and GTEx datasets, we identified genes associated with GBM prognosis. Molecular docking analysis suggested as a potential inhibitor. In vitro assays U-251MG cells were performed to assess Paromomycin’s cell viability, SUMOylation gene expression, IGF1R translocation using CCK8 assays, qRT-PCR, immunofluorescence. Results treatment led dose-dependent reduction colony formation, migration. It modulated SUMO1 expression decreased nuclear translocation, an effect reversible by inhibitor Trochostatin A (TSA), suggesting involvement SUMO1-regulated pathways. Conclusion highlights therapeutic agent for HDAC1-mediated influencing warranting further investigation its clinical application.

Язык: Английский

Процитировано

0

Cross-disease transcriptomic analysis reveals DOK3 and PAPOLA as therapeutic targets for neuroinflammatory and tumorigenic processes DOI Creative Commons
Xingqiao Wang,

Yusong Bian,

Wei-Guang Chen

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Дек. 12, 2024

Objective Subarachnoid hemorrhage (SAH) and tumorigenesis share numerous biological complexities; nevertheless, the specific gene expression profiles underlying mechanisms remain poorly understood. This study aims to identify differentially expressed genes (DEGs) that could serve as biomarkers for diagnosis prognosis. Methods Gene datasets (GSE122063, GSE13353, GSE161870) were analyzed using machine learning algorithms logistic regression DEGs associated with both SAH tumorigenesis. Lasso receiver operating characteristic (ROC) curve analysis employed evaluate classification accuracy of these genes. Validation critical was performed through pan-cancer experimental studies, focusing on role DOK3 in modulating inflammation oxidative stress U251MG glioblastoma BV2 microglia cells. Results Fifteen common identified, PAPOLA highlighted crucial implicated neurodegenerative processes. Experimental validation demonstrated overexpression significantly reduced pro-inflammatory cytokine levels markers while enhancing antioxidant enzyme activity. Additionally, influenced tumorigenic processes such apoptosis, cell cycle regulation, proliferation, effectively mitigating LPS-induced cytotoxicity microglial Conclusions play roles related neurodegeneration, presenting themselves potential prognostic therapeutic targets. Notably, exhibits an antitumor agent anti-inflammatory antioxidative properties, offering benefits cancer neuroinflammatory conditions.

Язык: Английский

Процитировано

0