LincRNAs MONC and MIR100HG act as oncogenes in acute megakaryoblastic leukemia

Molecular Cancer

Research

Dirk Reinhardt¹  Alexandra Streltsov¹  Jan-Henning Klusmann¹  Veera Raghavan Thangapandi¹  Stephan Emmrich¹  Franziska Schmidt¹ 

[1] Pediatric Hematology and Oncology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany;

关键词: Acute Myeloid Leukemia;    Down Syndrome;    K562 Cell;    Lock Nucleic Acid;    polyA Signal;   

DOI  :  10.1186/1476-4598-13-171

 received in 2014-04-07, accepted in 2014-07-03,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundLong non-coding RNAs (lncRNAs) are recognized as pivotal players during developmental ontogenesis and pathogenesis of cancer. The intronic microRNA (miRNA) clusters miR-99a ~ 125b-2 and miR-100 ~ 125b-1 promote progression of acute megakaryoblastic leukemia (AMKL), an aggressive form of hematologic cancers. The function of the lncRNA hostgenes MIR99AHG (alias MONC) and MIR100HG within this ncRNA ensemble remained elusive.ResultsHere we report that lncRNAs MONC and MIR100HG are highly expressed in AMKL blasts. The transcripts were mainly localized in the nucleus and their expression correlated with the corresponding miRNA clusters. Knockdown of MONC or MIR100HG impeded leukemic growth of AMKL cell lines and primary patient samples. The development of a lentiviral lncRNA vector to ectopically express lncRNAs without perturbing their secondary structure due to improper termination of the viral transcript, allowed us to study the function of MONC independent of the miRNAs in cord blood hematopoietic stem and progenitor cells (HSPCs). We could show that MONC interfered with hematopoietic lineage decisions and enhanced the proliferation of immature erythroid progenitor cells.ConclusionsOur study reveals an unprecedented function of lncRNAs MONC and MIR100HG as regulators of hematopoiesis and oncogenes in the development of myeloid leukemia.

【 授权许可】

Unknown   
© Emmrich et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.