PAICS-Driven Purine Biosynthesis and Its Prognostic Implications in Lung Adenocarcinoma: A Novel Risk Stratification Model and Therapeutic Insights DOI Creative Commons
Jinhui Liu, Qian Chen, Yannan Yang

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(5), P. 366 - 366

Published: May 16, 2025

Background: Lung adenocarcinoma is the most common NSCLC and associated with metabolic dysregulation. Purine biosynthesis, regulated by PAICS, plays a key role in tumor progression therapy resistance. Methods: We focused on LUAD using pan-cancer KEGG enrichment analyses. TCGA-LUAD three GEO datasets were analyzed to confirm prognostic relevance of purine biosynthesis. A model, Biosynthesis-Related Score (PBRS), was developed LASSO regression validated independent cohorts. Gene set variation analysis, immune profiling, mutational burden drug sensitivity analysis conducted. PAICS expression tissues, its assessed via proliferation migration assays. Results: PBRS classified patients into high-risk (PBRS-high) low-risk (PBRS-low) subgroups, distinct outcomes. PBRS-high showed cell cycle regulation DNA repair pathways had higher TMB, suggesting potential immunotherapy, although escape mechanisms may limit efficacy checkpoint inhibitors. PBRS-low more responsive overexpression correlated poor prognosis, while knockdown suppressed progression. Conclusion: tool LUAD, identifying who benefit from immunotherapy or DDR-targeted therapies. exhibit therapeutic target.

Language: Английский

Inhibition of RPA32 and Cytotoxic Effects of the Carnivorous Plant Sarracenia purpurea Root Extract in Non-Small-Cell Lung Cancer Cells DOI Creative Commons

Kuo-Ting Chang,

Yu‐Cheng Chen, Yi Lien

et al.

Plants, Journal Year: 2025, Volume and Issue: 14(10), P. 1426 - 1426

Published: May 9, 2025

The carnivorous plant Sarracenia purpurea has been traditionally used in various ethnobotanical applications, including treatments for type 2 diabetes and tuberculosis-like symptoms. This study investigates the cytotoxic effects of S. root extract (Sp-R) on human non-small-cell lung cancer (NSCLC) cell lines, H1975, H838, A549, focusing its impact survival, apoptosis, proliferation, migration. Additionally, ability to inhibit single-stranded DNA-binding activity RPA32 (huRPA32), a key protein DNA replication, was evaluated. Extracts from different parts (leaf, stem, root) were prepared using solvents (water, methanol, ethanol, acetone) screened apoptosis-inducing potential chromatin condensation assay. Among these, acetone-extracted fraction (Sp-R-A) exhibited most potent pro-apoptotic effects. MTT assay demonstrated dose-dependent effect NSCLC cells, with IC50 values 33.74 μg/mL 60.79 66.52 A549. Migration clonogenic assays further revealed that Sp-R-A significantly inhibited migration colony formation manner. Moreover, enhanced apoptosis when combined EGFR inhibitor afatinib, suggesting synergistic effect. electrophoretic mobility shift confirmed huRPA32, an 13.6 μg/mL. AlphaFold structural prediction molecular docking studies indicated major bioactive compounds purpurea, α-amyrin, ursolic acid, betulinaldehyde, strongly interact domain potentially contributing inhibitory Overall, these findings suggest huRPA32 is target anticancer against highlighted, supporting investigation into therapeutic applications.

Language: Английский

Citations

0
PAICS-Driven Purine Biosynthesis and Its Prognostic Implications in Lung Adenocarcinoma: A Novel Risk Stratification Model and Therapeutic Insights DOI Creative Commons
Jinhui Liu, Qian Chen, Yannan Yang

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(5), P. 366 - 366

Published: May 16, 2025

Background: Lung adenocarcinoma is the most common NSCLC and associated with metabolic dysregulation. Purine biosynthesis, regulated by PAICS, plays a key role in tumor progression therapy resistance. Methods: We focused on LUAD using pan-cancer KEGG enrichment analyses. TCGA-LUAD three GEO datasets were analyzed to confirm prognostic relevance of purine biosynthesis. A model, Biosynthesis-Related Score (PBRS), was developed LASSO regression validated independent cohorts. Gene set variation analysis, immune profiling, mutational burden drug sensitivity analysis conducted. PAICS expression tissues, its assessed via proliferation migration assays. Results: PBRS classified patients into high-risk (PBRS-high) low-risk (PBRS-low) subgroups, distinct outcomes. PBRS-high showed cell cycle regulation DNA repair pathways had higher TMB, suggesting potential immunotherapy, although escape mechanisms may limit efficacy checkpoint inhibitors. PBRS-low more responsive overexpression correlated poor prognosis, while knockdown suppressed progression. Conclusion: tool LUAD, identifying who benefit from immunotherapy or DDR-targeted therapies. exhibit therapeutic target.

Language: Английский

Citations

0