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Nat Commun ; 10(1): 5351, 2019 11 25.
Article in English | MEDLINE | ID: mdl-31767858

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.


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