Identification and Validation of Epithelial Cell Centre Regulatory Transcription Factors in the Gastric Cancer Microenvironment DOI Creative Commons
Guomiao Su, Juan Wang, Shiyue Liu

et al.

International Journal of General Medicine, Journal Year: 2024, Volume and Issue: Volume 17, P. 6567 - 6584

Published: Dec. 1, 2024

To identify the epithelial cell centre regulatory transcription factors in gastric cancer (GC) microenvironment and provide a new strategy for diagnosis treatment of GC. The GC single-cell dataset was downloaded from Gene Expression Omnibus (GEO) database. mechanisms both pan-cancer microenvironments were analysed using Cancer Genome Atlas (TGCA) Real-time quantitative PCR (RT-qPCR) used to determine mRNA expression levels Prospero homeobox gene 1 (PROX1) Endothelial PAS domain-containing protein (EPAS1) human mucosal normal line (GES-1) (AGS). Immunohistochemistry (IHC) amounts PROX1 EPAS1 adjacent tissues. patients' overall survival (OS) tracked through outpatient, Inpatient case inquiry, or phone follow-up. data GSE184198 re-annotated, resulting nine subsets: T cells (13364), NK (606), B (2525), Epithelial (2497), DC (1167), Fibroblast (372), (271), Neutrophils (246) Macrophage (420). Analysis subgroup signalling pathways revealed that communication intensity between smooth muscle highest. Transcription notably active cells. Cell analysis indicated IFNG may interact with IFNGR1/2 LIF IL6ST LIFR regulate downstream EPAS1. upregulated negatively correlated tumour mutation burden (TMB). They also exhibited high positive correlations immune checkpoints CTLA4 PDCD1LG2, as well chemokines CCL24 CXCL12 their receptors CCR3 CCR4. Additionally, positively immunosuppressive ADORA2A, CD160, IL10, TGFBR1, KDR CSF1R, immunostimulators CD276, PVR, TNFRSF25, ULBP1, ENTPD1. In tissues AGS, substantially expressed. meantime, they showed correlation clinicopathological features such TNM stage degree differentiation. patients, up-regulated group's prognosis noticeably poorer than down-regulated group's. are likely central environment, regulated by LIF. contribute progression modulating tumour's microenvironment.

Language: Английский

P53 and Rb Aberrations in Small Cell Lung Cancer (SCLC): From Molecular Mechanisms to Therapeutic Modulation DOI Open Access
Kostas A. Papavassiliou, Amalia A. Sofianidi, Vassiliki A. Gogou

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2479 - 2479

Published: Feb. 20, 2024

The genes coding for the tumor suppressors p53 and retinoblastoma (Rb) are inactivated in vast majority of small cell lung cancer (SCLC) tumors. Data support notion that these two deleterious genetic events represent initial steps development SCLC, making them essential a epithelial to progress toward acquisition malignant phenotype. With loss TP53 RB1, their broad suppressive functions eliminated normal is able proliferate indefinitely, escape entering into cellular senescence, evade death, no matter damage it has experienced. Within this setting, cells accumulate further oncogenic mutations well on way becoming SCLC cells. Understanding molecular mechanisms lesions effects within paramount importance, order tackle aggressive deadly cancer. present review summarizes current knowledge Rb aberrations, biological significance, prospective therapeutic potential, highlighting completed ongoing clinical trials with agents target downstream pathways.

Language: Английский

Citations

11
Specifying cellular context of transcription factor regulons for exploring context-specific gene regulation programs DOI Creative Commons
Mariia Minaeva, Júlia Domingo, Philipp Rentzsch

et al.

NAR Genomics and Bioinformatics, Journal Year: 2025, Volume and Issue: 7(1)

Published: Jan. 7, 2025

Abstract Understanding the role of transcription and factors (TFs) in cellular identity disease, such as cancer, is essential. However, comprehensive data resources for cell line-specific TF-to-target gene annotations are currently limited. To address this, we employed a straightforward method to define regulons that capture cell-specific aspects TF binding transcript expression levels. By integrating transcriptome data, generated 40 common lines comprising both proximal distal regulatory events. Through systematic benchmarking involving knockout experiments, demonstrated performance on par with state-of-the-art methods, our being easily applicable other types interest. We present case studies using three cancer single-cell datasets showcase utility these cell-type-specific exploring transcriptional dysregulation. In summary, this study provides valuable pipeline resource systematically regulations, emphasizing network analysis deciphering disease mechanisms.

Language: Английский

Citations

0
Identification of ETV4 as a prognostic biomarker and correlates with immune cell infiltration in head and neck squamous cell carcinoma DOI Creative Commons
Yulian Tang,

Wenyu Xie,

Ting Hu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 27, 2025

Head and neck squamous cell carcinoma (HNSC) is a common malignant tumor with high incidence mortality rates. ETS variant transcription factor 4 (ETV4), an important factor, plays key role in various cancers. However, the of ETV4 HNSC remains unclear. This study aimed to explore potential prognostic value oncogenic effects HNSC. We analyzed expression patients' data from TCGA database, alongside clinical pathological characteristics. The STRING GEPIA databases were utilized ETV4's interaction proteins related genes. Gene Set Enrichment Analysis (GSEA) was performed on stratified TCGA-HNSC cohort based levels. correlation between immune cells, checkpoints, regulatory genes further using R packages TISIDB database. Finally, knockdown nasopharyngeal cells (NPCs) siRNA evaluate proliferation, migration, invasion CCK-8, wound healing, clone formation, Transwell assays. significantly overexpressed closely characteristics prognosis. GSEA enrichment analysis showed significant multiple suppression pathways. Further immune-related indicated that negatively correlated most tumor-infiltrating lymphocyte type characteristic molecules, immunoinhibitors, activators MHC molecules. Knocking down inhibited migration NPCs. may serve as biomarker immunotherapy target High have negative effect level, matrix components

Language: Английский

Citations

0
Transcription factor NFKB1 mediates TUBB6 to promote the proliferation and suppress apoptosis in glioma via Wnt/β-catenin signaling pathway DOI Creative Commons
Yan Li, Ziyu Shao, Jun Jiang

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 1, 2025

Glioma remains one of the most challenging brain tumors with poor prognosis. In this study, we aimed to elucidate role TUBB6 in glioma and its potential as a diagnostic prognostic biomarker. Analysis GSE42656 TCGA datasets revealed that was significantly upregulated tissues compared normal tissues. The value demonstrated an area under curve (AUC) 0.702, suggesting it could be used biomarker differentiate gliomas Correlation analyses high expressions were associated advanced WHO grades, IDH mutation status, histological types glioma. Further investigation identified NFKB1 key transcription factor binds promoter region TUBB6, upregulating expression cells. Elevated levels overall survival disease-specific patients. Knockdown resulted reduced cells, confirming regulatory roles expression. Prognostic analysis using CGGA poorer (OS) (DSS) independent for both OS DSS. Additionally, pan-cancer dysregulated various tumor showed across multiple cancers. Functional enrichment TUBB6-associated differentially expressed genes indicated involvement immune response, extracellular matrix remodeling, cytokine signaling pathways. vitro experiments knockdown suppressed cell proliferation promoted apoptosis by regulating canonical Wnt/β-catenin pathway. Our findings suggest contributes malignancy through effects on conclusion, emerges promising diagnosis Its regulation pathways underscore therapeutic target treatment.

Language: Английский

Citations

0
Tumors and their microenvironments: Learning from pediatric brain pathologies DOI Creative Commons
Ruth Nussinov, Bengi Ruken Yavuz, Hyunbum Jang

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: 1880(3), P. 189328 - 189328

Published: April 18, 2025

Language: Английский

Citations

0
Role of Specificity Protein 1 (SP1) in Cardiovascular Diseases: Pathological Mechanisms and Therapeutic Potentials DOI Creative Commons
Jie Ding,

Aminah I. Fayyaz,

Yuchuan Ding

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 807 - 807

Published: July 7, 2024

In mammals, specificity protein 1 (SP1) was the first Cys2-His2 zinc finger transcription factor to be isolated within and Krüppel-like (Sp/KLF) gene family. SP1 regulates expression by binding Guanine–Cytosine (GC)-rich sequences on promoter regions of target genes, affecting various cellular processes. Additionally, activity is markedly influenced posttranslational modifications, such as phosphorylation, acetylation, glycosylation, proteolysis. implicated in regulation apoptosis, cell hypertrophy, inflammation, oxidative stress, lipid metabolism, plaque stabilization, endothelial dysfunction, fibrosis, calcification, other pathological These processes impact onset progression numerous cardiovascular disorders, including coronary heart disease, ischemia-reperfusion injury, cardiomyopathy, arrhythmia, vascular disease. emerges a potential for prevention therapeutic intervention cardiac ailments. this review, we delve into biological functions, pathophysiological mechanisms, clinical implications pathology offer valuable insights regulatory functions diseases unveil novel avenues treatment conditions.

Language: Английский

Citations

3
Emerging roles of long non-coding RNA FOXP4-AS1 in human cancers: From Molecular Biology to Clinical Application DOI Creative Commons

Jingjie Yang

Heliyon, Journal Year: 2024, Volume and Issue: 10(21), P. e39857 - e39857

Published: Oct. 28, 2024

Language: Английский

Citations

3
Advances in non-Hydroxamate based Histone Deacetylase Inhibitors as Anticancer Agents DOI Open Access

Nadine Wafik,

Maiy Y. Jaballah,

Rabah Serya

et al.

Archives of Pharmaceutical Sciences Ain Shams University, Journal Year: 2024, Volume and Issue: 8(1), P. 133 - 145

Published: April 9, 2024

The carcinogenesis process includes several epigenetic modifications that mainly target the silencing of tumor suppressor genes (TS genes) including ribonucleic acid (RNA) editing, deoxyribonucleic (DNA) hypermethylation and histone modification, either by methylation demethylation, or acetylation deacetylation. Histone deacetylation is one most important responsible for cancer development, thereby, design new selective deacetylase inhibitors (HDACIs) a promising chemotherapeutic target. Up to this time, all HDACIs approved are hydroxamic based. Yet, acids often show drawbacks upon administration, such as poor pharmacokinetic properties, selectivity, multiple toxicities. That's why urge emersion category compounds was crucial. Thereby, non-hydroxamate based attracted widespread attention being part biologically active safer alternative hydroxamate ones. In mini-review, we aim focus on HDACIs, specifically those used anticancer agents, concept behind their development.

Language: Английский

Citations

0
MiR-137 mediated high expression of TIGD1 promotes migration, invasion, and suppresses apoptosis of lung adenocarcinoma DOI Creative Commons

Yiqun Wei,

Runmiao Wu,

Shuanying Yang

et al.

Lung Cancer, Journal Year: 2024, Volume and Issue: 195, P. 107918 - 107918

Published: Aug. 5, 2024

Tigger transposable element-derived 1 (TIGD1) expression and its underlying functions regulatory mechanisms in lung adenocarcinoma (LUAD) remain unknown. Therefore, we intended to explore the expression, potential functions, of TIGD1 LUAD.

Language: Английский

Citations

0
ZNF775 inhibits MCF-7 breast cancer cell migration by downregulating Wnt5a DOI Creative Commons
Wei Gong,

Xin Zhu,

Wenwu Zhang

et al.

Advances in Cancer Biology - Metastasis, Journal Year: 2024, Volume and Issue: unknown, P. 100129 - 100129

Published: Oct. 1, 2024

Language: Английский

Citations

0