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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 tumor 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 MYC...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947006/ https://www.ncbi.nlm.nih.gov/pubmed/27383785 http://dx.doi.org/10.1038/nature18632 |
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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 Theiβen, 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_facet | Powers, John T Tsanov, Kaloyan M Pearson, Daniel S Roels, Frederik Spina, Catherine S Ebright, Richard Seligson, Marc de Soysa, Yvanka Cahan, Patrick Theiβen, 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 | PubMed |
description | Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumor 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. However, here we show that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN mRNA 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 pathogenesis with broad implications for cancer pathogenesis. |
format | Online Article Text |
id | pubmed-4947006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-49470062017-01-14 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 Theiβen, 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 Nature Article Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumor 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. However, here we show that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN mRNA 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 pathogenesis with broad implications for cancer pathogenesis. 2016-07-14 /pmc/articles/PMC4947006/ /pubmed/27383785 http://dx.doi.org/10.1038/nature18632 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Powers, John T Tsanov, Kaloyan M Pearson, Daniel S Roels, Frederik Spina, Catherine S Ebright, Richard Seligson, Marc de Soysa, Yvanka Cahan, Patrick Theiβen, 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947006/ https://www.ncbi.nlm.nih.gov/pubmed/27383785 http://dx.doi.org/10.1038/nature18632 |
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