dc.contributor.author | Powers, John T. | |
dc.contributor.author | Tsanov, Kaloyan M. | |
dc.contributor.author | Pearson, Daniel S. | |
dc.contributor.author | Roels, Frederik | |
dc.contributor.author | Spina, Catherine S. | |
dc.contributor.author | Ebright, Richard | |
dc.contributor.author | Seligson, Marc | |
dc.contributor.author | de Soysa, Yvanka | |
dc.contributor.author | Cahan, Patrick | |
dc.contributor.author | Theißen, Jessica | |
dc.contributor.author | Tu, Ho-Chou | |
dc.contributor.author | Han, Areum | |
dc.contributor.author | Kurek, Kyle C. | |
dc.contributor.author | LaPier, Grace S. | |
dc.contributor.author | Osborne, Jihan K. | |
dc.contributor.author | Ross, Samantha J. | |
dc.contributor.author | Cesana, Marcella | |
dc.contributor.author | Collins, James J. | |
dc.contributor.author | Berthold, Frank | |
dc.contributor.author | Daley, George Q. | |
dc.date.accessioned | 2017-04-06T19:26:43Z | |
dc.date.available | 2017-04-06T19:26:43Z | |
dc.date.issued | 2016-07 | |
dc.date.submitted | 2015-02 | |
dc.identifier.issn | 0028-0836 | |
dc.identifier.issn | 1476-4687 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/107912 | |
dc.description.abstract | Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis. | en_US |
dc.description.sponsorship | United States. National Institutes of Health (R01GM107536) | en_US |
dc.description.sponsorship | Alex's Lemonade Stand Foundation | en_US |
dc.description.sponsorship | Howard Hughes Medical Institute | en_US |
dc.description.sponsorship | Boston Children's Hospital. Manton Center for Orphan Disease Research | en_US |
dc.description.sponsorship | National Institute of General Medical Sciences (U.S.) (T32GM007753) | en_US |
dc.language.iso | en_US | |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/nature18632 | en_US |
dc.rights | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. | en_US |
dc.source | PMC | en_US |
dc.title | Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Powers, John T., Kaloyan M. Tsanov, Daniel S. Pearson, Frederik Roels, Catherine S. Spina, Richard Ebright, Marc Seligson, et al. “Multiple Mechanisms Disrupt the Let-7 microRNA Family in Neuroblastoma.” Nature 535, no. 7611 (July 6, 2016): 246–251. © 2016 Rights Managed by Nature Publishing Group | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | |
dc.contributor.mitauthor | Collins, James J. | |
dc.relation.journal | Nature | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Powers, John T.; Tsanov, Kaloyan M.; Pearson, Daniel S.; Roels, Frederik; Spina, Catherine S.; Ebright, Richard; Seligson, Marc; de Soysa, Yvanka; Cahan, Patrick; Theißen, Jessica; Tu, Ho-Chou; Han, Areum; Kurek, Kyle C.; LaPier, Grace S.; Osborne, Jihan K.; Ross, Samantha J.; Cesana, Marcella; Collins, James J.; Berthold, Frank; Daley, George Q. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-5560-8246 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |