Assessing TGF-β Prognostic Model Predictions for Chemotherapy Response and Oncogenic Role of FKBP1A in Liver Cancer DOI Creative Commons

Weimei Chen,

Qinghe Que,

Rongrong Zhong

и другие.

Current Pharmaceutical Design, Год журнала: 2024, Номер 30(39), С. 3131 - 3152

Опубликована: Авг. 26, 2024

Background: The Transforming Growth Factor-Beta (TGF-β) signaling pathway plays a crucial role in the pathogenesis of diseases. This study aimed to identify differentially expressed TGF-β-related genes liver cancer patients and correlate these findings with clinical features immune signatures. Methods: TCGA-STAD LIRI-JP cohorts were utilized for comprehensive analysis TGF-β- related genes. Differential gene expression, functional enrichment, survival analysis, machine learning techniques employed develop prognostic model based on signature (TGFBRS). Results: We developed expression levels nine indicates that higher TGFBRS values are associated poorer prognosis, tumor grades, more advanced pathological stages, resistance chemotherapy. Additionally, TGFBRS-High subtype was characterized by elevated immune-suppressive cells increased checkpoint molecules. Using Gradient Boosting Decision Tree (GBDT) approach, FKBP1A identified as playing significant cancer. Notably, knocking down significantly inhibited proliferation metastatic capabilities both vitro vivo. Conclusion: Our highlights potential predicting chemotherapy responses shaping microenvironment results promising molecular target developing preventive therapeutic strategies against could potentially guide personalized treatment improve prognosis patients.

Язык: Английский

TOP2A inhibition and its cellular effects related to cell cycle checkpoint adaptation pathway DOI Creative Commons
M. López,

María Ángeles Fernández-Mimbrera,

E. Gollini

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 30, 2025

Abstract In this study, we investigate the G2 checkpoint activated by chromosome entanglements, so-called Decatenation Checkpoint (DC), which can be TOP2A catalytic inhibition. Specifically, focus on spontaneous ability of cells to bypass or override checkpoint, referred as adaptation. Some factors involved in adapting are p53 and MCPH1. Using cellular models depleted both MCPH1 hTERT-RPE1 cells, analyzed cell cycle dynamics adaptation, segregation defects, apoptosis rate, transcriptional changes related prolonged exposure inhibitors. Our findings reveal that altered MCPH1-depleted compared control cells. We found depletion restore robustness DC a p53-negative background. Furthermore, research highlights differential effects poisons inhibitors outcomes profiles. By examining different mechanisms inhibition their impact processes, study contributes deeper understanding regulation physiological implications adaptation non-carcinogenic lines.

Язык: Английский

Процитировано

1
A Chemotherapy Response-Related Gene Signature and DNAJC8 as Key Mediators of Hepatocellular Carcinoma Progression and Drug Resistance DOI Creative Commons
Yan Ye, Yanmei Zeng, Shan Huang

и другие.

Journal of Hepatocellular Carcinoma, Год журнала: 2025, Номер Volume 12, С. 579 - 595

Опубликована: Март 1, 2025

Chemotherapy resistance in hepatocellular carcinoma presents a significant challenge to improved patient outcomes. Identifying genes associated with chemotherapy response can enhance treatment strategies and prognostic models. We analyzed the expression of response-related gene using TCGA GSE109211 cohorts. constructed model Least Absolute Shrinkage Selection Operator (LASSO) analysis assessed its efficacy Kaplan-Meier survival analysis. Additionally, we evaluated immune landscape mutation profiles between different (CRRG) subtypes. DNAJC8's role cell functions was further explored through knockdown experiments vitro vivo. Differential identified 220 common response. The incorporating seven key efficiently distinguished responders from non-responders indicated poorer overall for CRRG-high subtype. CRRG value correlated tumor stage grade, showed distinct patterns subtype exhibited an immune-suppressive phenotype higher PD-L1 CTLA-4. High DNAJC8 linked poor prognosis multiple Knocking down significantly inhibited proliferation, migration, invasion, reduced sorafenib IC50. seven-gene model, particularly DNAJC8, holds potential predicting serves as therapeutic target carcinoma.

Язык: Английский

Процитировано

0
Identification of key biomarker genes in liver hepatocellular carcinoma and kidney renal clear cell carcinoma progression: A shared high-throughput screening and molecular docking method with potentials for targeted therapeutic interventions DOI
Maisha Tasneem, Shipan Das Gupta,

Md Jubair Ahmed Jony

и другие.

Journal of Genetic Engineering and Biotechnology, Год журнала: 2025, Номер 23(2), С. 100497 - 100497

Опубликована: Апрель 22, 2025

Язык: Английский

Процитировано

0
Skin Telocytes Could Fundament the Cellular Mechanisms of Wound Healing in Platelet-Rich Plasma Administration DOI Creative Commons
Catalin G. Manole, Vlad Mihai Voiculescu,

Cristina Soare

и другие.

Cells, Год журнала: 2024, Номер 13(16), С. 1321 - 1321

Опубликована: Авг. 8, 2024

For more than 40 years, autologous platelet concentrates have been used in clinical medicine. Since the first formula used, namely platelet-rich plasma (PRP), other experimented with, including fibrin and concentrated growth factor. Platelet three standard characteristics: they act as scaffolds, serve a source of factors cytokines, contain live cells. PRP has become extensively regenerative medicine for successful treatment variety (non-)dermatological conditions like alopecies, acne scars, skin burns, ulcers, muscle, cartilage, bone repair, an adjuvant post-surgery wound healing, with obvious benefits terms functionality aesthetic recovery affected tissues/organs. These indications were well documented, large amount evidence already published supporting efficacy this method. The primordial principle behind minimally invasive treatments is usage patient’s own platelets. transplantation thrombocytes are significant, representing fast economic method that requires only basic equipment training, it biocompatible, thus being low risk patient (infection immunological reactions can be virtually disregarded). Usually, structural applying attributed to fibroblasts only, considered most numerous cell population within interstitium. However, apparent simplistic explanation still eluding those different types interstitial cells (distinct from fibroblasts) residing stromal tissue, e.g., telocytes (TCs). Moreover, dermal TCs documented potential angiogenesis (extra-cutaneous, but also skin), their implication few dermatological was attested described ultrastructurally immunophenotypically. Interestingly, biochemically consists series factors, molecules, which proven positive expression. Thus, attractive hypothesize document any tissular collaboration between cutaneous administered local recovery/repair/regeneration. Therefore, could perceived missing link necessary provide solid good results achieved by administering skin-repairing processes.

Язык: Английский

Процитировано

3
Assessing TGF-β Prognostic Model Predictions for Chemotherapy Response and Oncogenic Role of FKBP1A in Liver Cancer DOI Creative Commons

Weimei Chen,

Qinghe Que,

Rongrong Zhong

и другие.

Current Pharmaceutical Design, Год журнала: 2024, Номер 30(39), С. 3131 - 3152

Опубликована: Авг. 26, 2024

Background: The Transforming Growth Factor-Beta (TGF-β) signaling pathway plays a crucial role in the pathogenesis of diseases. This study aimed to identify differentially expressed TGF-β-related genes liver cancer patients and correlate these findings with clinical features immune signatures. Methods: TCGA-STAD LIRI-JP cohorts were utilized for comprehensive analysis TGF-β- related genes. Differential gene expression, functional enrichment, survival analysis, machine learning techniques employed develop prognostic model based on signature (TGFBRS). Results: We developed expression levels nine indicates that higher TGFBRS values are associated poorer prognosis, tumor grades, more advanced pathological stages, resistance chemotherapy. Additionally, TGFBRS-High subtype was characterized by elevated immune-suppressive cells increased checkpoint molecules. Using Gradient Boosting Decision Tree (GBDT) approach, FKBP1A identified as playing significant cancer. Notably, knocking down significantly inhibited proliferation metastatic capabilities both vitro vivo. Conclusion: Our highlights potential predicting chemotherapy responses shaping microenvironment results promising molecular target developing preventive therapeutic strategies against could potentially guide personalized treatment improve prognosis patients.

Язык: Английский

Процитировано

0