Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma
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 MY...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/107912 https://orcid.org/0000-0002-5560-8246 |
| _version_ | 1811085804740542464 |
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| author | 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. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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. |
| author_sort | Powers, John T. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:15:56Z |
| format | Article |
| id | mit-1721.1/107912 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:15:56Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1079122024-06-26T19:03:59Z Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma 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. Massachusetts Institute of Technology. Department of Biological Engineering Collins, James J. 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. United States. National Institutes of Health (R01GM107536) Alex's Lemonade Stand Foundation Howard Hughes Medical Institute Boston Children's Hospital. Manton Center for Orphan Disease Research National Institute of General Medical Sciences (U.S.) (T32GM007753) 2017-04-06T19:26:43Z 2017-04-06T19:26:43Z 2016-07 2015-02 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/107912 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 https://orcid.org/0000-0002-5560-8246 en_US http://dx.doi.org/10.1038/nature18632 Nature 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. application/pdf Nature Publishing Group PMC |
| spellingShingle | 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. Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma |
| title | Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma |
| title_full | Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma |
| title_fullStr | Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma |
| title_full_unstemmed | Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma |
| title_short | Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma |
| title_sort | multiple mechanisms disrupt the let 7 microrna family in neuroblastoma |
| url | http://hdl.handle.net/1721.1/107912 https://orcid.org/0000-0002-5560-8246 |
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