The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
The Oncogenic MicroRNA miR-22 Targets the TET2 Tumor Suppressor to Promote Hematopoietic Stem Cell Self-Renewal and Transformation
Open accessAbstract
SUMMARY 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-incuced 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.
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Cited by
TET-mediated active DNA demethylation: mechanism, function and beyond
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“Distributions of 5fC and 5caC were determined by antibody (5fC/5caC DIP) (Shen et al., 2013) or chemical tagging (fC-Seal) (Song et al., 2013a) methods.”
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Self-citationMicroRNAs as regulatory elements in immune system logic
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Drug Resistance Driven by Cancer Stem Cells and Their Niche
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Metadata
- 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.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 13
- Issue
- 1
- Pages
- 87-101
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2053930062
- Cited by
- 326
- References
- 46
- FWCI
- 14.59
- Type
- journal article
- Language
- en
- Open access
- bronze
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- 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. (2013). The Oncogenic MicroRNA miR-22 Targets the TET2 Tumor Suppressor to Promote Hematopoietic Stem Cell Self-Renewal and Transformation. Cell Stem Cell. https://doi.org/10.1016/j.stem.2013.06.003
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