Inhibition of pre-miRNA-21 processing by bPGN leads to cell cycle arrest in colorectal cancer cells

Authors

• JS Matarlo
• LRH Krumpe
• SS Kurian
• WF Heinz
• SJ Lockett
• BR O'Keefe

Abstract

Growing evidence shows that mature microRNA (miR) and precursor miRNA (pre-miR) can be targets for specific small-molecule inhibitors. miR-21 is a 22-nucleotide regulatory oncogenic miRNA that is over-expressed in most cancers and is a regulator of numerous oncogenic and tumor suppressor genes such as PDCD4, PTEN, CDC25A, SKP2, and MYC. Thus, modulation of oncogenic miR-21 expression can be a promising strategy for future drug discovery with broad therapeutic applications. Here, we identified the natural product butylcycloheptyl prodiginine (bPGN), as a novel small-molecule inhibitor of pre-miR-21 processing in colorectal cancer cells. We show that bPGN can interact with pre-miR-21 at low micromolar affinity and can selectively downregulate expression of cancer-associated target genes. We propose that the natural product class prodiginine can be a new and promising chemical pharmacophore for the development of future RNA-interacting cancer therapeutics.

Scientific Focus Area: Chemical Biology

This page was last updated on Friday, March 26, 2021