Integrative analysis of m6A-SNPs and single-cell RNA sequencing reveals key drivers of endocrine combined with CDK4/6 inhibitor therapy resistance in ER+ breast cancer DOI Creative Commons

Ruijie Ming,

Han Zhang, Huan Wu

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 15, 2025

Background Endocrine therapy combined with CDK4/6 inhibitors remains a standard treatment for ER+ breast cancer, yet resistance is prevalent challenge. This study explores the role of N6-methyladenosine (m6A) modifications, influenced by m6A-SNPs, in shaping resistance, utilizing single-cell RNA sequencing to delineate underlying molecular mechanisms. Methods We integrated genome-wide association data transcriptomic profiles from cancer patients, focusing on differences between resistant and sensitive responses inhibitors. m6A-SNPs were identified analyzed their impact gene expression interactions RNA-binding proteins, particular focus roles within key cellular pathways. Results The crucial associated resistance. Notably, changes FILIP1L TOM1L1, related these SNPs, mapped using pseudotime trajectory analysis, which traced evolution states. TOM1L1 exhibited dynamic along trajectory, correlating significant shifts cell fate decisions. These findings underscore potential as mediators development particularly through involvement PI3K-Akt Wnt signaling pathways, critical progression drug Conclusion Our emphasize importance influencing cancer. regulation developmental tumor cells sensitivity provides insights into complexity results pave way developing targeted therapies that modify m6A-driven offering new strategies counteract improve patient outcomes.

Язык: Английский

Chronic Stress Mediates Inflammatory Cytokines Alterations and Its Role in Tumorigenesis DOI Creative Commons
Zhihan Liu, Lei Meng, Yanxia Bai

и другие.

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 1067 - 1090

Опубликована: Янв. 1, 2025

Introduction: Prolonged psychological stress is closely associated with cancer due to its role in promoting the release of hormones through sustained activation sympathetic-adrenal-medullary system.These interact receptors on inflammatory cells, leading key signaling pathways, including transcription factors signal transducer and activator 3 (STAT-3) kappa-light-chain-enhancer activated B cells (NF-κB).These drive production pro-inflammatory substances, such as interleukin-6 (IL-6) tumor necrosis factor-α (TNF-α), which can influence initiation progression cancer.Purpose: This article aims summarize how chronic environment induced by promotes initiation, progression, invasion cancer.By enhancing our understanding complex mechanisms contributes cancer, we hope identify new targets for prevention treatment.Conclusion: Chronic establishes an microenvironment activating STAT-3 NF-κB cells.This ongoing inflammation further enhances activity these factors, serve multiple roles: they act proinflammatory agents maintaining inflammation; oncogenic premalignant initiation; pro-differentiation tumor-infiltrating immune facilitating progression.Additionally, impact varies among different types individual responses stress, highlighting complexity stress-related mechanisms.Ultimately, this dynamic interplay creates a feedback loop involving IL-6, STAT-3, TNF-α-NF-κB within microenvironment, mediating intricate interactions between inflammation, immunity, cancer.

Язык: Английский

Процитировано

1
Potential of Bioactive Compounds In Coleus amboinicus, Lour., Leaves Against Breast Cancer By Assessment Using A Network Pharmacology Approach and Cytotoxic Test DOI
Winarto Haryadi, Kasta Gurning, Jajah Fachiroh

и другие.

Journal of Multidisciplinary Applied Natural Science, Год журнала: 2025, Номер 5(1), С. 267 - 287

Опубликована: Янв. 26, 2025

Breast cancer is a disease that significantly contributes to global women death. The study aims conduct in vitro activity testing and assessment with bioinformatics approach using pharmacological network of bioactive compounds from bangun-bangun (Coleus amboinicus) leaves extract as breast drug. methods used are extraction by maceration partition, identification analysis the Liquid Chromatography High-Resolution Mass Spectrometry (LC-HRMS) instrument, cytotoxic cells (MCF-7) normal (CV-1) MTT method, through pharmacology. results test ethyl acetate provided better IC50 value 102.30 457.09 µg/mL against MCF-7 CV-1 cells. selectivity index 4.23 indicates potential for further development treatment cancer. chemical compound content show various types anticancer; networks pharmacology pathways provides predictions signal transducer activator transcription 3 (STAT3) protein main therapeutic mechanism target treatment. This initial information research on utilizing C. amboinicus an alternative

Язык: Английский

Процитировано

0
Integrative analysis of m6A-SNPs and single-cell RNA sequencing reveals key drivers of endocrine combined with CDK4/6 inhibitor therapy resistance in ER+ breast cancer DOI Creative Commons

Ruijie Ming,

Han Zhang, Huan Wu

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 15, 2025

Background Endocrine therapy combined with CDK4/6 inhibitors remains a standard treatment for ER+ breast cancer, yet resistance is prevalent challenge. This study explores the role of N6-methyladenosine (m6A) modifications, influenced by m6A-SNPs, in shaping resistance, utilizing single-cell RNA sequencing to delineate underlying molecular mechanisms. Methods We integrated genome-wide association data transcriptomic profiles from cancer patients, focusing on differences between resistant and sensitive responses inhibitors. m6A-SNPs were identified analyzed their impact gene expression interactions RNA-binding proteins, particular focus roles within key cellular pathways. Results The crucial associated resistance. Notably, changes FILIP1L TOM1L1, related these SNPs, mapped using pseudotime trajectory analysis, which traced evolution states. TOM1L1 exhibited dynamic along trajectory, correlating significant shifts cell fate decisions. These findings underscore potential as mediators development particularly through involvement PI3K-Akt Wnt signaling pathways, critical progression drug Conclusion Our emphasize importance influencing cancer. regulation developmental tumor cells sensitivity provides insights into complexity results pave way developing targeted therapies that modify m6A-driven offering new strategies counteract improve patient outcomes.

Язык: Английский

Процитировано

0