| First Author | Conkrite K | Year | 2011 |
| Journal | Genes Dev | Volume | 25 |
| Issue | 16 | Pages | 1734-45 |
| PubMed ID | 21816922 | Mgi Jnum | J:174680 |
| Mgi Id | MGI:5140623 | Doi | 10.1101/gad.17027411 |
| Citation | Conkrite K, et al. (2011) miR-17~92 cooperates with RB pathway mutations to promote retinoblastoma. Genes Dev 25(16):1734-45 |
| abstractText | The miR-17 approximately 92 cluster is a potent microRNA-encoding oncogene. Here, we show that miR-17 approximately 92 synergizes with loss of Rb family members to promote retinoblastoma. We observed miR-17 approximately 92 genomic amplifications in murine retinoblastoma and high expression of miR-17 approximately 92 in human retinoblastoma. While miR-17 approximately 92 was dispensable for mouse retinal development, miR-17 approximately 92 overexpression, together with deletion of Rb and p107, led to rapid emergence of retinoblastoma with frequent metastasis to the brain. miR-17 approximately 92 oncogenic function in retinoblastoma was not mediated by a miR-19/PTEN axis toward apoptosis suppression, as found in lymphoma/leukemia models. Instead, miR-17 approximately 92 increased the proliferative capacity of Rb/p107-deficient retinal cells. We found that deletion of Rb family members led to compensatory up-regulation of the cyclin-dependent kinase inhibitor p21Cip1. miR-17 approximately 92 overexpression counteracted p21Cip1 up-regulation, promoted proliferation, and drove retinoblastoma formation. These results demonstrate that the oncogenic determinants of miR-17 approximately 92 are context-specific and provide new insights into miR-17 approximately 92 function as an RB-collaborating gene in cancer. |
