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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

LincRNAs MONC and MIR100HG act as oncogenes in acute megakaryoblastic leukemia

Authors: Stephan Emmrich, Alexandra Streltsov, Franziska Schmidt, Veera Raghavan Thangapandi, Dirk Reinhardt, Jan-Henning Klusmann

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

Long 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.

Results

Here 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.

Conclusions

Our study reveals an unprecedented function of lncRNAs MONC and MIR100HG as regulators of hematopoiesis and oncogenes in the development of myeloid leukemia.
Appendix
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Metadata
Title
LincRNAs MONC and MIR100HG act as oncogenes in acute megakaryoblastic leukemia
Authors
Stephan Emmrich
Alexandra Streltsov
Franziska Schmidt
Veera Raghavan Thangapandi
Dirk Reinhardt
Jan-Henning Klusmann
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-171

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