A 3,4-diamino-substituted coumarin derivative as a TRBP inhibitor suppresses tumor growth in breast cancer by inducing cellular senescence.

ABSTRACT: Transactivation response RNA-binding protein 2 (TRBP) mediates microRNA (miRNA) biogenesis and regulates messenger RNA (mRNA) stability. It is a pivotal regulator of post-transcriptional gene expression, influencing processes including cellular senescence and tumorigenesis. Elevated TRBP expression correlates with poor prognosis in breast cancer, underscoring its potential as a therapeutic target. We identified a 3,4-diamino-substituted coumarin derivative (3ai), a novel small-molecule compound inhibitor of miR-21 biogenesis. Compound 3ai increased the expression of tumor-suppressor proteins targeted by miR-21. Further mechanistic studies revealed that 3ai binds TRBP and disrupts the biogenesis of senescence-associated miRNAs. This interaction induces cell cycle arrest and DNA damage in tu

SUBMITTER: Zhao D 

PROVIDER: S-EPMC12616159 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature