title: LincRNAs MONC and MIR100HG act as oncogenes in acute megakaryoblastic leukemia.
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.
authors.forename: Stephan
authors.initials: S
authors.lastname: Emmrich
authors.forename: Alexandra
authors.initials: A
authors.lastname: Streltsov
authors.forename: Franziska
authors.initials: F
authors.lastname: Schmidt
authors.forename: Veera Raghavan
authors.initials: VR
authors.lastname: Thangapandi
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.affiliation: Pediatric Hematology and Oncology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany. Klusmann.Jan-Henning@mh-hannover.de.
authors.forename: Jan-Henning
authors.initials: JH
authors.lastname: Klusmann
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D003001:Cloning, Molecular; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000378:metabolism; D006413:Hematopoietic System / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D009857:Oncogenes; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering