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

• Published in: Nature communications Vol. 10; no. 1; pp. 5351 - 15
• Main Authors: Papaioannou, Dimitrios, Petri, Andreas, Dovey, Oliver M., Terreri, Sara, Wang, Eric, Collins, Frances A., Woodward, Lauren A., Walker, Allison E., Nicolet, Deedra, Pepe, Felice, 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, Xiaoqing, Kohlschmidt, Jessica, Archer, Kellie J., Freitas, Michael A., Zheng, Yi, Lee, Robert J., Aifantis, Iannis, Vassiliou, George, Singh, Guramrit, Kauppinen, Sakari, Bloomfield, Clara D., Dorrance, Adrienne M., Garzon, Ramiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.11.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 14/1; 38/109; 38/22; 38/89; 38/90; 38/91; 42/89; 45/15; 45/88; 45/91; 631/337; 631/337/384; 631/337/572; 631/67; 692/4017; Acute Disease; Acute myeloid leukemia; Animals; Cell Line, Tumor; Cell Proliferation; Deoxyribonucleic acid; DNA; EBP1 protein; ErbB-3 protein; HEK293 Cells; Humanities and Social Sciences; Humans; K562 Cells; Leukemia; Leukemia, Myeloid - genetics; Leukemia, Myeloid - pathology; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; multidisciplinary; Mutation; Myeloid leukemia; Non-coding RNA; Nuclear Proteins - genetics; Nucleophosmin; Protein biosynthesis; Protein Biosynthesis - genetics; Protein synthesis; Proteins; Ribonucleic acid; Ribosomal DNA; RNA; RNA, Long Noncoding - genetics; RNA, Ribosomal - genetics; rRNA; Science; Science (multidisciplinary); THP-1 Cells; Transcription; Transcription, Genetic; Transplantation, Heterologous
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13259-2

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 ( NPM1 mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1 mut 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. LncRNAs at the HOX gene locus are increased in expression in NPM1 mutant acute myeloid leukemia. In this study, the authors show that one such lncRNA, HOX3B-AS3, has a role in regulating gene transcription and protein synthesis in leukemia cells.