Toxicology in Vitro, Год журнала: 2024, Номер 99, С. 105875 - 105875
Опубликована: Июнь 12, 2024
Язык: Английский
Advanced Science, Год журнала: 2025, Номер unknown
Опубликована: Янв. 22, 2025
Abstract A cell fate change such as tumorigenesis incurs critical transition. It remains a longstanding challenge whether the underlying mechanism can be unraveled and molecular switch that reverse transition is found. Here systems framework, REVERT, presented with which reconstruct core regulatory network model reversion based on single‐cell transcriptome data over process identified. The usefulness of REVERT demonstrated by applying it to patient‐derived matched organoids colon cancer normal colon. generic framework applied investigate various phenomena.
Язык: Английский
Процитировано
1
Cancers, Год журнала: 2024, Номер 16(6), С. 1237 - 1237
Опубликована: Март 21, 2024
During the last decade, we have witnessed several milestones in treatment of various resistant cancers including immunotherapeutic strategies that proven to be superior conventional options, such as chemotherapy and radiation. This approach utilizes host’s immune response, which is triggered by cancer cells expressing tumor-associated antigens or neoantigens. The responsive cytotoxic CD8+ T specifically target kill tumor cells, leading regression prolongation survival some cancers; however, may exhibit resistance due inactivation anti-tumor cells. One mechanism become dysfunctional through activation inhibitory receptor programmed death-1 (PD-1) corresponding (or other microenvironment (TME)) express death ligand-1 (PD-L1). Hence, blocking PD-1/PD-L1 interaction via specific monoclonal antibodies (mAbs) restores cells’ functions, regression. Accordingly, Food Drug Administration (FDA) has approved checkpoint act inhibitors. Their clinical use cancers, metastatic melanoma non-small-cell lung (NSCLC), shown significant responses. We investigated an alternative prevent expression PD-L1 on targeting oncogenic transcription factor Yin Yang 1 (YY1), a known overexpressed many cancers. report regulation YY1 at transcriptional, post-transcriptional, post-translational levels, resulting restoration functions. performed bioinformatic analyses further explore relationship between both corroborate these findings. In addition its PD-L1, anti-cancer activities, proliferation cell viability, invasion, epithelial–mesenchymal transition (EMT), metastasis, chemo-immuno-resistance. Thus, will multitude activities obliteration activities. Various are proposed selectively human present promising novel therapeutic for treating unresponsive phenotypes. These findings underscore distinct regulatory roles (CD274) progression response.
Язык: Английский
Процитировано
6
Heliyon, Год журнала: 2024, Номер 10(10), С. e30780 - e30780
Опубликована: Май 1, 2024
Cisplatin-based chemotherapy is the current standard care for lung cancer patients; however, drug resistance frequently develops during treatment, thereby limiting therapeutic efficacy.The molecular mechanisms underlying cisplatin remain elusive. In this study, we conducted an analysis of microarray data from Gene Expression Omnibus (GEO) database under accession numbers GSE21656, which encompassed expression profiling cisplatin-resistant H460 (DDP-H460)and parental cells (H460). Subsequently, calculated differentially expressed genes (DEGs) between DDP-H460 and H460. Ontology (GO) enrichment Kyoto Encyclopedia Genes Genomes (KEGG) pathway DEGs demonstrated significant impact on Rap1, PI3K/AKT MAPK signaling pathways. Moreover, protein interaction (PPI) network identified PRKCA, DET1, UBE2N as hub that potentially contribute predominantly to resistance. Ultimately, PRKCA was selected validation due its prognostic effect, predicts unfavorable overall survival disease-free in patients with cancer. Network The Cancer Genome Atlas (TCGA) revealed a strong gene-level correlation TP53, CDKN2A, BYR2, TTN, KRAS, PIK3CA; whereas at level, it exhibited high EGFR, Lck, Bcl2, Syk. vitro experiments
Язык: Английский
Процитировано
6
Cell Death and Disease, Год журнала: 2024, Номер 15(5)
Опубликована: Май 20, 2024
Colorectal cancer (CRC) remains a significant global health issue with high incidence and mortality. Yin Yang 1 (YY1) is powerful transcription factor that acts dual roles in gene activation repression. High expression level of YY1 has been reported CRC, indicating the existence stable factors CRC cells. We aimed to identify key molecules underlying mechanisms responsible for stabilizing CRC. Mass spectrometry analysis was utilized USP7 as potential molecule interacted YY1. Mechanically, stabilizes at protein by interfering its K63 linkage ubiquitination. exerts oncogenic function through transcriptionally activating TRIAP1 but suppressing LC3B. In addition, pathological level, there positive correlation between budding This study revealed intricate interplay suggesting they could serve novel therapeutic targets or predictive biomarkers patients.
Язык: Английский
Процитировано
5
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(24), С. 17238 - 17238
Опубликована: Дек. 7, 2023
Metabolic reprogramming, especially reprogrammed glucose metabolism, is a well-known cancer hallmark related to various characteristics of tumor cells, including proliferation, survival, metastasis, and drug resistance. Glucose-6-phosphate dehydrogenase (G6PD) the first rate-limiting enzyme pentose phosphate pathway (PPP), branch glycolysis, that converts glucose-6-phosphate (G6P) into 6-phosphogluconolactone (6PGL). Furthermore, PPP produces ribose-5-phosphate (R5P), which provides sugar-phosphate backbones for nucleotide synthesis as well nicotinamide adenine dinucleotide (NADPH), an important cellular reductant. Several studies have shown enhanced G6PD expression flux in their correlation with progression through regulation, reprogramming sustaining proliferative signaling, resisting cell death, activating invasion metastasis. Inhibiting could suppress promote reverse chemoresistance, inhibit suggesting potential target anti-tumor therapeutic strategies. Indeed, while challenges-including side effects-still remain, small-molecule inhibitors showing effect either when used alone or combination other drugs been developed. This review overview structural significance G6PD, its role regulation development progression, strategies explored relation G6PD-targeted therapy.
Язык: Английский
Процитировано
11
Phytomedicine, Год журнала: 2024, Номер 130, С. 155734 - 155734
Опубликована: Май 12, 2024
Язык: Английский
Процитировано
4
Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 3067 - 3091
Опубликована: Март 1, 2025
High transcription levels are essential for cancer cells to maintain their malignant phenotype. While RNA polymerases (POLRs) have been implicated in various transcriptional mechanisms, impact on the tumor microenvironment (TME) remains poorly understood. We analyzed publicly available pan-cancer cohorts evaluate expression and genomic alterations of POLRs. Focusing head neck squamous cell carcinoma (HNSC), we integrated bulk sequencing, single-cell, spatial transcriptome data identify POLR2C patterns its potential regulation by Yin Yang 1 (YY1). In vitro vivo experiments were conducted validate functional role YY1-POLR2C axis proliferation immune modulation. POLRs found be aberrantly expressed cancers associated with alterations. HNSC, POLR up-regulation was linked poor prognostic features. significantly up-regulated cells, appeared transcriptionally regulated YY1. Functional studies demonstrated that drives cell-cycle dysregulation HNSC. Additionally, high negatively correlated infiltration facilitated evasion. Mechanistically, mediated frequent interactions between potentially contributing resistance immunotherapy. This study highlights dual promoting shaping an immunosuppressive TME. POLR2C, YY1, emerges as a critical mediator HNSC promising target precision therapies.
Язык: Английский
Процитировано
0
Cancer Reports, Год журнала: 2025, Номер 8(3)
Опубликована: Март 1, 2025
ABSTRACT Background Emerging evidence indicates that the transcription factor Yin Yang 1 (YY1) plays a critical role in carcinogenesis and progression of various human malignancies. YY1 is highly expressed gastric cancer (GC), raising interest its GC. Aims This study aims to analyze cancer, investigate effect on tumor microenvironment, assess potential as prognostic marker. Methods Results Transcriptomic data clinical information from GC patients were obtained TCGA UCSC databases. expression was analyzed using R “limma” package. Gene ontology (GO) enrichment Kyoto Encyclopedia Genes Genomes (KEGG) pathway analyses performed with online tool clusterProfiler. The relationship between levels microenvironment examined different risk groups patients. Additionally, YY1‐positive staining 26 samples measured ImageJ software. Co‐expression analysis used identify genes associated YY1, model built optimized. showed significantly overexpressed 415 ( p < 0.001) poorer survival outcomes = 0.043). GO KEGG involved key biological processes disease. Higher correlated lower stromal immune cell content microenvironment. Immunohistochemical confirmed overexpression tissues compared normal 0.0293). Positive correlations observed MTA1, TTL15, HNRNPU, WDR20, PPP4R3A. model, which included (risk score AUC 0.690), predicted patient better than other variables. Conclusion These findings suggest an important development Targeting may be treatment strategy for
Язык: Английский
Процитировано
0
Biochemical Pharmacology, Год журнала: 2025, Номер unknown, С. 116919 - 116919
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Reproductive Biology, Год журнала: 2025, Номер 25(2), С. 101020 - 101020
Опубликована: Апрель 19, 2025
Язык: Английский
Процитировано
0