The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

Nat Commun. 2019 Nov 25;10(1):5351. doi: 10.1038/s41467-019-13259-2.

Abstract

Long non-coding RNAs (lncRNAs) are important regulatory molecules that are implicated in cellular physiology and pathology. In this work, we dissect the functional role of the HOXB-AS3 lncRNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 is shown to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism, HOXB-AS3 regulates ribosomal RNA transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • HEK293 Cells
  • Humans
  • K562 Cells
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / pathology
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Mutation*
  • Nuclear Proteins / genetics*
  • Nucleophosmin
  • Protein Biosynthesis / genetics
  • RNA, Long Noncoding / genetics*
  • RNA, Ribosomal / genetics*
  • THP-1 Cells
  • Transcription, Genetic*
  • Transplantation, Heterologous

Substances

  • NPM1 protein, human
  • Npm1 protein, mouse
  • Nuclear Proteins
  • RNA, Long Noncoding
  • RNA, Ribosomal
  • Nucleophosmin