The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation Journal Article


Authors: Song, S. J.; Ito, K.; Ala, U.; Kats, L.; Webster, K.; Sun, S. M.; Jongen-Lavrencic, M.; Manova-Todorova, K.; Teruya-Feldstein, J.; Avigan, D. E.; Delwel, R.; Pandolfi, P. P.
Article Title: The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation
Abstract: MicroRNAs are frequently deregulated in cancer. Here we show that miR-22 is upregulated in myelodysplastic syndrome (MDS) and leukemia and its aberrant expression correlates with poor survival. To explore its role in hematopoietic stem cell function and malignancy, we generated transgenic mice conditionally expressing miR-22 in the hematopoietic compartment. These mice displayed reduced levels of global 5-hydroxymethylcytosine (5-hmC) and increased hematopoietic stem cell self-renewal-accompanied by defective differentiation. Conversely, miR-22 inhibition blocked proliferation in both mouse and human leukemic cells. Over time, miR-22 transgenic mice developed MDS and hematological malignancies. We also identify TET2 as a key target of miR-22 in this context. Ectopic expression of TET2 suppressed the miR-22-induced phenotypes. Downregulation of TET2 protein also correlated with poor clinical outcomes and miR-22 overexpression in MDS patients. Our results therefore identify miR-22 as a potent proto-oncogene and suggest that aberrations in the miR-22/TET2 regulatory network are common in hematopoietic malignancies.
Keywords: dna methylation; differentiation; mutations; expression; malignancies; acute myeloid-leukemia; myeloproliferative neoplasms; cancers; lna; mutant tet2
Journal Title: Cell Stem Cell
Volume: 13
Issue: 1
ISSN: 1934-5909
Publisher: Cell Press  
Date Published: 2013-07-03
Start Page: 87
End Page: 101
Language: English
ACCESSION: WOS:000329570100015
DOI: 10.1016/j.stem.2013.06.003
PROVIDER: wos
PMCID: PMC3767186
PUBMED: 23827711
Notes: Article -- Source: Wos
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  1. Julie T Feldstein
    293 Feldstein