Precise Small Molecule Degradation of a Noncoding RNA Identifies Cellular Binding Sites and Modulates an Oncogenic Phenotype.

ABSTRACT: Herein, we describe the precise cellular destruction of an oncogenic noncoding RNA with a small molecule-bleomycin A5 conjugate, affording reversal of phenotype and a facile method to map the cellular binding sites of a small molecule. In particular, bleomycin A5 was coupled to a small molecule that selectively binds the microRNA-96 hairpin precursor (pri-miR-96). By coupling of bleomycin A5's free amine to the RNA binder, its affinity for binding to pri-miR-96 is >100-fold stronger than to DNA and the compound selectively cleaves pri-miR-96 in triple negative breast cancer (TNBC) cells. Indeed, selective cleavage of pri-miR-96 enhanced expression of FOXO1 protein, a pro-apoptotic transcription factor that miR-96 silences, and triggered apoptosis in TNBC cells. No effects were observed in

SUBMITTER: Li Y 

PROVIDER: S-EPMC6340300 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature