Oncogenic Potential of the miR-106-363 Cluster and Its Implication in Human T-Cell Leukemia
Copyright policy )Oncogenic Potential of the miR-106-363 Cluster and Its Implication in Human T-Cell Leukemia
Abstract We previously reported the identification of the Kis2 common retrovirus integration site, located on mouse chromosome X, in radiation leukemia virus–induced T-cell leukemias. Tumors with a provirus at the Kis2 locus overexpressed a novel noncoding RNA (ncRNA) with a complex splicing pattern and no polyA tail. Database upgrade revealed the presence of a microRNA (miRNA) cluster, miR-106-363, just downstream of the Kis2 ncRNAs. We found that Kis2 ncRNAs are the pri-miRNA of miR-106-363, and we present evidence that Kis2 ncRNA overexpression in mouse tumors results in miR-106a, miR-19b-2, miR-92-2, and miR-20b accumulation. We show the oncogenic potential of those miRNAs in anchorage independence assay and confirm pri-miR-106-363 overexpression in 46% of human T-cell leukemias tested. This overexpression contributes in rising miR-92 and miR-19 levels, as this is the case for miR-17-92 cluster overexpression. Furthermore, we identified myosin regulatory light chain–interacting protein, retinoblastoma-binding protein 1-like, and possibly homeodomain-interacting protein kinase 3 as target genes of this miRNA cluster, which establishes a link between these genes and T-cell leukemia for the first time. [Cancer Res 2007;67(12):5699–707]
- Université du Québec à Montréal Canada
- University of Quebec Canada
Radiation Leukemia Virus, Leukemia, T-Cell, RNA, Untranslated, Base Sequence, Blotting, Western, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Gene Expression, Retinoblastoma-Like Protein p107, Oncogenes, Protein Serine-Threonine Kinases, Blotting, Northern, Gene Expression Regulation, Neoplastic, Mice, MicroRNAs, Cell Transformation, Neoplastic, NIH 3T3 Cells, Animals, Humans, Retroviridae Infections
Radiation Leukemia Virus, Leukemia, T-Cell, RNA, Untranslated, Base Sequence, Blotting, Western, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Gene Expression, Retinoblastoma-Like Protein p107, Oncogenes, Protein Serine-Threonine Kinases, Blotting, Northern, Gene Expression Regulation, Neoplastic, Mice, MicroRNAs, Cell Transformation, Neoplastic, NIH 3T3 Cells, Animals, Humans, Retroviridae Infections
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