Oncogenic potential of the miR-106-363 cluster and its implication in human T-cell leukemia

Cancer Res. 2007 Jun 15;67(12):5699-707. doi: 10.1158/0008-5472.CAN-06-4478.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • Cell Transformation, Neoplastic / genetics*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Leukemia, T-Cell / genetics*
  • Leukemia, T-Cell / virology
  • Mice
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Oncogenes / genetics*
  • Protein-Serine-Threonine Kinases / genetics
  • RNA, Untranslated
  • Radiation Leukemia Virus
  • Retinoblastoma-Like Protein p107 / genetics
  • Retroviridae Infections / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Virus Infections / genetics
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs
  • RNA, Untranslated
  • Retinoblastoma-Like Protein p107
  • MYLIP protein, human
  • Ubiquitin-Protein Ligases
  • HIPK3 protein, human
  • Protein-Serine-Threonine Kinases