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

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.

SUBMITTER: Papaioannou D 

PROVIDER: S-EPMC6877618 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Papaioannou Dimitrios D   Petri Andreas A   Dovey Oliver M OM   Terreri Sara S   Wang Eric E   Collins Frances A FA   Woodward Lauren A LA   Walker Allison E AE   Nicolet Deedra D   Pepe Felice F   Kumchala Prasanthi P   Bill Marius M   Walker Christopher J CJ   Karunasiri Malith M   Mrózek Krzysztof K   Gardner Miranda L ML   Camilotto Virginia V   Zitzer Nina N   Cooper Jonathan L JL   Cai Xiongwei X   Rong-Mullins Xiaoqing X   Kohlschmidt Jessica J   Archer Kellie J KJ   Freitas Michael A MA   Zheng Yi Y   Lee Robert J RJ   Aifantis Iannis I   Vassiliou George G   Singh Guramrit G   Kauppinen Sakari S   Bloomfield Clara D CD   Dorrance Adrienne M AM   Garzon Ramiro R  

Nature communications 20191125 1

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, HO  ...[more]

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