A novel peptide CP29L, selected from the phage displayed cyclic random heptapeptide library, demonstrates its potent inhibitory effects to liver cancer HCCLM3 cells by targeting FOXM1

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177246 - 177246

Published: Jan. 1, 2025

Language: Английский

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Potential of the nanoplatform and PROTAC interface to achieve targeted protein degradation through the Ubiquitin–Proteasome system

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 267, P. 116168 - 116168

Published: Feb. 1, 2024

Language: Английский

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EWS/FLI1 Characterization, Activation, Repression, Target Genes and Therapeutic Opportunities in Ewing Sarcoma

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15173 - 15173

Published: Oct. 14, 2023

Despite their clonal origins, tumors eventually develop into complex communities made up of phenotypically different cell subpopulations, according to mounting evidence. Tumor cell-intrinsic programming and signals from geographically temporally changing microenvironments both contribute this variability. Furthermore, the mutational load is typically lacking in childhood malignancies adult cancers, they still exhibit high cellular heterogeneity levels largely mediated by epigenetic mechanisms. Ewing sarcomas represent highly aggressive affecting bone soft tissue, primarily afflicting adolescents. Unfortunately, outlook for patients facing relapsed or metastatic disease grim. These are fueled a distinctive fusion event involving an FET protein ETS family transcription factor, with most prevalent being EWS/FLI1. originating common driver mutation, sarcoma cells display significant variations transcriptional activity, within among tumors. Recent research has pinpointed distinct activities as principal source heterogeneity, resulting markedly diverse phenotypes. In review, we aim characterize role EWS/FLI exploring its general mechanism activation elucidating implications tumor heterogeneity. Additionally, delve potential therapeutic opportunities target aberrant context treatment.

Language: Английский

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Novel 8-Methoxycoumarin-3-Carboxamides with potent anticancer activity against liver cancer via targeting caspase-3/7 and β-tubulin polymerization

BMC Chemistry, Journal Year: 2023, Volume and Issue: 17(1)

Published: Dec. 2, 2023

In the present study, we explored potential of coumarin-based compounds, known for their potent anticancer properties, by designing and synthesizing a novel category 8-methoxycoumarin-3-carboxamides. Our aim was to investigate antiproliferative activity against liver cancer cells. Toward this, developed versatile synthetic approach produce series 8-methoxycoumarin-3-carboxamide analogues with meticulous structural features. Assessment demonstrated significant inhibitory effects on growth HepG2 cells, widely studied cell line. Among screened compound 5 exhibited most among compounds (IC50 = 0.9 µM), outperforming drug staurosporine 8.4 while showing minimal impact normal The flow cytometric analysis revealed that induces cycle arrest during G1/S phase triggers apoptosis in cells increasing percentage arrested G2/M pre-G1 phases. Annexin V-FITC/PI screening further supported induction without necrosis. Further, ability activate caspase3/7 protein substantially inhibited β-tubulin polymerization Finally, molecular modelling affirmed high binding affinity toward active cavity protein, suggesting its mechanistic involvement. Collectively, our findings highlight therapeutic presented class coumarin analogues, especially 5, as promising candidates development effective anti-hepatocellular carcinoma agents.

Language: Английский

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Molecular biomarkers of progression in non-muscle-invasive bladder cancer — beyond conventional risk stratification

Nature Reviews Urology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 2, 2024

Language: Английский

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The transcription factor FOXQ1 in cancer

Cancer and Metastasis Reviews, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 8, 2025

Language: Английский

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Integrated bioinformatics analysis to explore potential therapeutic targets and drugs for small cell carcinoma of the esophagus

Frontiers in Bioinformatics, Journal Year: 2025, Volume and Issue: 5

Published: Jan. 28, 2025

Background Small cell carcinoma of the esophagus (SCCE) is a rare form esophageal cancer, which also belongs to category neuroendocrine malignant tumors, with low incidence but high aggressiveness, and very poor prognosis for patients. Currently, there lack unique staging treatment guidelines SCCE. Therefore, deeper understanding therapeutic targets mechanisms underlying its occurrence development great importance early diagnosis, identification potential agents improvement Methods Firstly, dataset SCCE was downloaded from GEO database GEO2R tool employed analysis differentially expressed genes (DEGs). GO KEGG DEGs were carried out by using Bioinformatics OmicStudio tools. Then, up- down-regulated intersected oncogenes tumor suppressor respectively, obtain onco/tumor in The STRING conduct protein-protein interaction (PPI) genes, network further constructed Cytoscape, hub obtained through Cytohubba plugin. In addition, miRDB, miRwalk, Targetscan, OncomiR, starbase, Lncbase used predict miRNAs lncRNAs that regulate ceRNA built based on this. Transcription factor-miRNA co-regulatory analyzed NetworkAnalyst embellished Cytoscape. Finally, drugs may target searched DGIdb ConnectivityMAP, docking verification performed Schrodinger. Results A total 820 upregulated 716 downregulated, these, 54 identified as 85 genes. Seven PPI network, AURKA, BIRC5 , CDK1 EZH2 FOXM1 KLF4 UBE2C . Furthermore, 38 filtered molecular results score AURKA multiple (<6). crizotinib lapatinib CDK1, rucaparib EZH2, lowest energy all results. Conclusion are SCCE, among them, be drugs. Crizotinib, lapatinib, can act above inhibit progression play role.

Language: Английский

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FOXM1-Driven CKS1B Upregulation Promotes Pancreatic Cancer Progression and Therapeutic Resistance

International Journal of Biological Sciences, Journal Year: 2025, Volume and Issue: 21(3), P. 1047 - 1064

Published: Jan. 13, 2025

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with limited treatment options. Investigating novel therapeutic targets and understanding mechanisms of chemoresistance are crucial for improving patient outcomes. This study investigated the role CKS1B in PDAC carcinogenesis, stemness chemoresistance, explores underlying driving its upregulation. The findings may provide insights potential strategies PDAC. Methods: expression was analyzed tissues cell lines, impact on proliferation, migration, apoptosis, chemosensitivity were evaluated by using vitro vivo models, mechanistic connection to transcription factor FOXM1 explored molecular biology methods. Results: significantly upregulated correlated poor survival. promoted inhibited apoptosis. Expression enhanced properties pancreatic cancer. knockdown sensitized cells gemcitabine oxaliplatin. Mechanistically, is transcriptionally regulated FOXM1, establishing FOXM1-CKS1B signaling axis that regulates stemness, drug resistance Conclusions: Our strongly suggest plays critical progression, chemoresistance. Targeting represents promising strategy patients.

Language: Английский

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Machine learning identification of a novel vasculogenic mimicry-related signature and FOXM1’s role in promoting vasculogenic mimicry in clear cell renal cell carcinoma

Translational Oncology, Journal Year: 2025, Volume and Issue: 53, P. 102312 - 102312

Published: Feb. 3, 2025

Language: Английский

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NEK2 promotes the progression of osteosarcoma through the AKT/p-AKT pathway and interacts with FoxM1

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(4)

Published: March 19, 2025

Language: Английский

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