Screening of four signature genes for clinical testing through bioinformatics and in vitro methods in head and neck squamous cell carcinoma.
Muhammad Rizwan Javed,

Rimsha Sadia Bukhari,

Rubab Rasool

et al.

PubMed, Journal Year: 2023, Volume and Issue: 13(5), P. 1826 - 1844

Published: Jan. 1, 2023

Head and neck squamous cell carcinoma (HNSC) is the 6th most common cancer around globe; its underlying molecular mechanisms accurate markers are still lacking. In this study, we explored hub genes their potential signaling pathways through which these participate in development of HNSC. The GSE23036 gene microarray dataset was attained from GEO (Gene Expression Omnibus) database. Hub were identified via Cytohubba plug-in application Cytoscape. Cancer Genome Atlas (TCGA) datasets lines (HOK FuDu) used to evaluate expression variations genes. Moreover, promoter methylation, genetic alteration, enrichment, miRNA network, immunocyte infiltration analysis also performed confirm oncogenic role biomarker HNSC patients. Based on results, four genes, including KNTC1 (Kinetochore Associated 1), CEP55 (Centrosomal protein 55 kDa), AURKA (Aurora A Kinase), ECT2 (Epithelial Cell Transforming 2), with highest degree scores denoted as All significantly up-regulated clinical samples relative counterparts. Overexpression KNTC1, CEP55, AURKA, associated poor survival various parameters Methylation targeted bisulfite sequencing HOK FuDu revealed that overexpression due hypomethylation. higher expressions positively correlated abundance CD4+ T cells macrophage while reduction CD8+ samples. Finally, enrichment showed all involved "nucleoplasm, centrosome, mitotic spindle, cytosol" pathways. conclusion, could be biomarkers for patients provide a novel insight into diagnosis treatment disease.

Language: Английский

A biological guide to glycosaminoglycans: current perspectives and pending questions DOI Creative Commons
Sylvie Ricard‐Blum, Romain R. Vivès, Liliana Schaefer

et al.

FEBS Journal, Journal Year: 2024, Volume and Issue: 291(15), P. 3331 - 3366

Published: March 18, 2024

Mammalian glycosaminoglycans (GAGs), except hyaluronan (HA), are sulfated polysaccharides that covalently attached to core proteins form proteoglycans (PGs). This article summarizes key biological findings for the most widespread GAGs, namely HA, chondroitin sulfate/dermatan sulfate (CS/DS), keratan (KS), and heparan (HS). It focuses on major processes remain be deciphered get a comprehensive view of mechanisms mediating GAG functions. They include regulation biosynthesis postsynthetic modifications in heparin (HP) HS, composition, heterogeneity, function tetrasaccharide linkage region its role disease, functional characterization new PGs recently identified by glycoproteomics, selectivity interactions mediated chains, display chains at cell surface their impact availability activity soluble ligands, move through glycocalyx layer reach receptors, human profile health roles GAGs particular (syndecans, decorin, biglycan) involved cancer, inflammation, fibrosis, possible use as disease biomarkers, design inhibitors targeting biosynthetic enzymes GAG-protein develop novel therapeutic approaches.

Language: Английский

Citations

28
Seize the engine: Emerging cell cycle targets in breast cancer DOI Creative Commons
Jesús Fuentes‐Antrás, Philippe L. Bédard, David W. Cescon

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 1, 2024

Language: Английский

Citations

12
Identidication of novel biomarkers in non-small cell lung cancer using machine learning DOI Creative Commons
Fangwei Wang, Qisheng Su, Chaoqian Li

et al.

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Oct. 6, 2022

Lung cancer is one of the leading causes cancer-related deaths worldwide, and non-small cell lung (NSCLC) accounts for a large proportion cases, with few diagnostic therapeutic targets currently available NSCLC. This study aimed to identify specific biomarkers We obtained three gene-expression profiles from Gene Expression Omnibus database (GSE18842, GSE21933, GSE32863) screened differentially expressed genes (DEGs) between NSCLC normal tissue. Enrichment analyses were performed using Ontology, Disease Kyoto Encyclopedia Genes Genomes. Machine learning methods used optimal least absolute shrinkage selection operator logistic regression, support vector machine recursive feature elimination. CIBERSORT was assess immune infiltration in correlation cells. Finally, western blot, small interfering RNA, Cholecystokinin-8, transwell assays, biological functions high predictive value validated. A total 371 DEGs (165 up-regulated 206 down-regulated genes) identified, enrichment analysis revealed that these might be linked development progression ABCA8, ADAMTS8, ASPA, CEP55, FHL1, PYCR1, RAMP3, TPX2 identified as novel Monocytes most visible activated cells The knockdown gene, biomarker value, inhibited A549 proliferation migration. eight potential Further, gene may target

Language: Английский

Citations

28
Unraveling Therapeutic Opportunities and the Diagnostic Potential of microRNAs for Human Lung Cancer DOI Creative Commons
Osama Sweef, Elsayed Zaabout,

Ahmed Bakheet

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(8), P. 2061 - 2061

Published: July 31, 2023

Lung cancer is a major public health problem and leading cause of cancer-related deaths worldwide. Despite advances in treatment options, the five-year survival rate for lung patients remains low, emphasizing urgent need innovative diagnostic therapeutic strategies. MicroRNAs (miRNAs) have emerged as potential biomarkers targets due to their crucial roles regulating cell proliferation, differentiation, apoptosis. For example, miR-34a miR-150, once delivered via liposomes or nanoparticles, can inhibit tumor growth by downregulating critical promoting genes. Conversely, miR-21 miR-155, frequently overexpressed cancer, are associated with increased invasion, chemotherapy resistance. In this review, we summarize current knowledge miRNAs carcinogenesis, especially those induced exposure environmental pollutants, namely, arsenic benzopyrene, which account up 1/10 cases. We then discuss recent miRNA-based therapeutics diagnostics. Such information will provide new insights into pathogenesis modalities based on miRNAs.

Language: Английский

Citations

15
Discovery of the First Potent, Selective, and In Vivo Efficacious Polo-like Kinase 4 Proteolysis Targeting Chimera Degrader for the Treatment of TRIM37-Amplified Breast Cancer DOI
Yin Sun,

Yanli Xue,

Pengkun Sun

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(12), P. 8200 - 8221

Published: June 6, 2023

Polo-like kinase 4 (PLK4) is a master regulator of centriole replication and has been proposed as therapeutic target for multiple cancers, especially TRIM37-amplified breast cancer. The development novel effective strategies cancer therapy challenging extremely desirable. Herein, structure-activity relationship (SAR) study with an emphasis on exploring different linker lengths compositions was performed to report the discovery characterization SP27 first selective PLK4 proteolysis targeting chimera (PROTAC) degrader. exhibited degradation, more potent inhibition cell growth, efficient precision-therapeutic effect in MCF-7 line than conventional inhibitor CZS-035. Moreover, showed 149% bioavailability after intraperitoneal administration PK studies antitumor efficacy vivo. demonstrated practicality importance PROTAC paved way studying PLK4-dependent biological functions treat

Language: Английский

Citations

14
Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA DOI Creative Commons
Menghua Chen, Huijun Zhu, Jian Li

et al.

Annals of Medicine, Journal Year: 2024, Volume and Issue: 56(1)

Published: May 13, 2024

AURKA is a threonine or serine kinase that needs to be activated by TPX2, Bora and other factors. located on chromosome 20 amplified overexpressed in many human cancers, such as breast cancer. regulates some basic cellular processes, this regulation realized

Language: Английский

Citations

4
Drivers of centrosome abnormalities: senescence progression and tumor immune escape DOI
Tao Jiang,

Hua Jin,

Xintong Ji

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Molecular genetic predictors of progression of triple negative breast cancer DOI Creative Commons

I. S. Panchenko,

В. В. Родионов, В. В. Кометова

et al.

Siberian Journal of Oncology, Journal Year: 2025, Volume and Issue: 24(1), P. 70 - 78

Published: March 18, 2025

Introduction . Triple-negative breast cancer (TNBC) is a group of malignant tumors with poor prognosis and varying molecular genetic characteristics. In TNBC, genes determine whether patients belong to clusters that differ in prognosis. There are not enough studies consider as risk factors for progression. The aim this study was identify TNBC which associated high progression, evaluate their prognostic significance. Material methods This included 246 TNBC. Forty-five performing various functions were used panel genes. research technique consisted preliminary RNA isolation followed by real-time cDNA amplification using PCR. Mean gene expression levels calculated measures central tendency the numerical value 95 CI. significance influence on progression (locoregional recurrence or distant metastasis) assessed formation linear discriminant function construction ROC curve. relationship between clinical morphological parameters correlation analysis (Pearson’s χ 2 Spearman’s ρ test). After determining threshold values subsequent ranking into groups low levels, an survival formed carried out (Kaplan-Meier curves). When comparing curves, long-rank test used. Results Two genes: PGR (p=0.007) AR (p=0.001), locoregional relapse, 1 gene: FOXA1 , metastasis selected analysis. Statistically significant (p<0.05) correlations expressions tumor grade level proliferative activity (Ki67) found. Low (≤-6.4), (≤-4.7), (≤-4.4) improved overall survival. Conclusion markers marker metastasis. significantly correlated Ki67. favorable

Language: Английский

Citations

0
A Liquid–Liquid Phase Separation-Related Index Associate with Biochemical Recurrence and Tumor Immune Environment of Prostate Cancer Patients DOI Open Access
Qi You,

Jia‐Yin Chen,

Xiaohui Wu

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5515 - 5515

Published: March 14, 2023

To identify liquid-liquid phase separation (LLPS)-related molecular clusters, and to develop validate a novel index based on LLPS for predicting the prognosis of prostate cancer (PCa) patients. We download clinical transcriptome data PCa from TCGA GEO database. The LLPS-related genes (LRGs) were extracted PhaSepDB. Consensus clustering analysis was used subtypes PCa. LASSO cox regression performed establish biochemical recurrence (BCR)-free survival (BCRFS). Preliminary experimental verification performed. initially identified total 102 differentially expressed LRGs Three related identified. Moreover, we established signature BCRFS Compared low-risk patients in training cohort, testing cohort validating high-risk populations meant higher risk BCR significantly poorer BCRFS. area under receiver operating characteristic curve 0.728, 0.762, 0.741 at 1 year cohort. Additionally, subgroup indicated that this especially suitable with age ≤ 65, T stage III-IV, N0 or cluster 1. FUS, which potential biomarker separation, preliminarily verified. This study successfully developed three signature, well

Language: Английский

Citations

8
Centrosomes and associated proteins in pathogenesis and treatment of breast cancer DOI Creative Commons

Harjot Athwal,

Arpitha Kochiyanil,

Vasudeva Bhat

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: March 28, 2024

Breast cancer is the most prevalent malignancy among women worldwide. Despite significant advances in treatment, it remains one of leading causes female mortality. The inability to effectively treat advanced and/or treatment-resistant breast demonstrates need develop novel treatment strategies and targeted therapies. Centrosomes their associated proteins have been shown play key roles pathogenesis thus represent promising targets for drug biomarker development. are fundamental cellular structures mammalian cell that responsible error-free execution division. Centrosome amplification aberrant expression its such as Polo-like kinases (PLKs), Aurora (AURKs) Cyclin-dependent (CDKs) observed various cancers, including cancer. These aberrations thought cause improper chromosomal segregation during mitosis, instability uncontrolled division, allowing cells acquire new genetic changes result evasion death promotion tumor formation. Various chemical compounds developed against PLKs AURKs meaningful antitumorigenic effects vitro vivo . mechanism action these inhibitors likely related exacerbation numerical genomic instability, aneuploidy or polyploidy. Furthermore, growing evidence enhanced when specific centrosome-associated used combination with either radiation chemotherapy drugs This review focuses on current knowledge regarding centrosome utility treatment.

Language: Английский

Citations

3