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

Thursday, September 13, 2018 — Poster Session III

12:00 p.m. – 1:30 p.m.
FAES Terrace
NCI
CHEMBIO-5

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.

Category: Chemical Biology