Modulation of oncogenic miRNA biogenesis using functionalized polyamines.

ABSTRACT: MicroRNAs are key factors in the regulation of gene expression and their deregulation has been directly linked to various pathologies such as cancer. The use of small molecules to tackle the overexpression of oncogenic miRNAs has proved its efficacy and holds the promise for therapeutic applications. Here we describe the screening of a 640-compound library and the identification of polyamine derivatives interfering with in vitro Dicer-mediated processing of the oncogenic miR-372 precursor (pre-miR-372). The most active inhibitor is a spermine-amidine conjugate that binds to the pre-miR-372 with a K_D of 0.15 µM, and inhibits its in vitro processing with a IC₅₀ of 1.06 µM. The inhibition of miR-372 biogenesis was confirmed in gastric cancer cells overexpressing miR-372

SUBMITTER: Staedel C 

PROVIDER: S-EPMC5786041 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature