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

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

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