| First Author | Murphy BL | Year | 2013 |
| Journal | Cancer Res | Volume | 73 |
| Issue | 23 | Pages | 7068-78 |
| PubMed ID | 24145352 | Mgi Jnum | J:206525 |
| Mgi Id | MGI:5551339 | Doi | 10.1158/0008-5472.CAN-13-0927 |
| Citation | Murphy BL, et al. (2013) Silencing of the miR-17~92 cluster family inhibits medulloblastoma progression. Cancer Res 73(23):7068-78 |
| abstractText | Medulloblastoma, originating in the cerebellum, is the most common malignant brain tumor in children. Medulloblastoma consists of four major groups where constitutive activation of the Sonic Hedgehog (SHH) signaling pathway is a hallmark of one group. Mouse and human SHH medulloblastomas exhibit increased expression of microRNAs encoded by the miR-17~92 and miR-106b~25 clusters compared with granule progenitors and postmitotic granule neurons. Here, we assessed the therapeutic potential of 8-mer seed-targeting locked nucleic acid (LNA)-modified anti-miR oligonucleotides, termed tiny LNAs, that inhibit microRNA seed families expressed by miR-17~92 and miR-106b~25 in two mouse models of SHH medulloblastomas. We found that tumor cells (medulloblastoma cells) passively took up 8-mer LNA-anti-miRs and specifically inhibited targeted microRNA seed-sharing family members. Inhibition of miR-17 and miR-19a seed families by anti-miR-17 and anti-miR-19, respectively, resulted in diminished tumor cell proliferation in vitro. Treatment of mice with systemic delivery of anti-miR-17 and anti-miR-19 reduced tumor growth in flank and brain allografts in vivo and prolonged the survival of mice with intracranial transplants, suggesting that inhibition of the miR-17~92 cluster family by 8-mer LNA-anti-miRs might be considered for the treatment of SHH medulloblastomas. |
