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

Author:

Papaioannou Dimitrios,Petri AndreasORCID,Dovey Oliver M.,Terreri Sara,Wang Eric,Collins Frances A.,Woodward Lauren A.,Walker Allison E.,Nicolet Deedra,Pepe FeliceORCID,Kumchala Prasanthi,Bill Marius,Walker Christopher J.,Karunasiri Malith,Mrózek Krzysztof,Gardner Miranda L.,Camilotto Virginia,Zitzer Nina,Cooper Jonathan L.,Cai Xiongwei,Rong-Mullins XiaoqingORCID,Kohlschmidt Jessica,Archer Kellie J.ORCID,Freitas Michael A.,Zheng Yi,Lee Robert J.,Aifantis Iannis,Vassiliou GeorgeORCID,Singh GuramritORCID,Kauppinen Sakari,Bloomfield Clara D.ORCID,Dorrance Adrienne M.,Garzon Ramiro

Abstract

AbstractLong 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.

Funder

U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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