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

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

Author information

1
The Ohio State University, Comprehensive Cancer Center, Columbus, OH, USA.
2
Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.
3
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
4
Institute of Genetics and Biophysics (IGB-ABT), National Council of Research (CNR), Naples, Italy.
5
Department of Pathology, New York University School of Medicine, New York, NY, USA.
6
Department of Molecular Genetics, Center for RNA Biology, The Ohio State University, Columbus, OH, USA.
7
Alliance for Clinical Trials in Oncology Statistics and Data Center, The Ohio State University, Columbus, OH, USA.
8
Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
9
Department of Molecular Medicine, University of Pavia, Pavia, USA.
10
Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
11
Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, OH, USA.
12
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
13
Department of Haematology, Cambridge University Hospitals NHS Trust, Cambridge, UK.
14
The Ohio State University, Comprehensive Cancer Center, Columbus, OH, USA. ramiro.garzon@osumc.edu.

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.

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