Oncogenic potential of the miR-106-363 cluster and its implication in human T-cell leukemia.
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.
Landais
Séverine
S
Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Université du Québec à Montréal, Montreal, Quebec, Canada.
Landry
Sébastien
S
Legault
Philippe
P
Rassart
Eric
E
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000821:virology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009857:Oncogenes / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D022661:RNA, Untranslated; D016721:Radiation Leukemia Virus; D050720:Retinoblastoma-Like Protein p107 / Q000235:genetics; D012192:Retroviridae Infections / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014412:Tumor Virus Infections / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D022661:RNA, Untranslated; D050720:Retinoblastoma-Like Protein p107; C403126:MYLIP protein, human; D044767:Ubiquitin-Protein Ligases; C109102:HIPK3 protein, human; D017346:Protein Serine-Threonine Kinases