Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia. Academic Article uri icon

Overview

abstract

  • The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08-2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI's oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.

authors

publication date

  • June 19, 2019

Research

keywords

  • Gene Expression Regulation, Leukemic
  • Leukemia, Experimental
  • Leukemia, Myeloid, Acute
  • Pteridines
  • RNA-Binding Proteins

Identity

PubMed Central ID

  • PMC6584500

Scopus Document Identifier

  • 85067488438

Digital Object Identifier (DOI)

  • 10.1021/ct200463m

PubMed ID

  • 31217428

Additional Document Info

volume

  • 10

issue

  • 1