Powers, John T., Tsanov, Kaloyan M., Pearson, Daniel S., Roels, Frederik, Spina, Catherine S., Ebright, Richard, Seligson, Marc, de Soysa, Yvanka, Cahan, Patrick ORCID: 0000-0003-3652-2540, 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 and Daley, George Q. (2016). Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma. Nature, 535 (7611). S. 246 - 264. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Powers, John T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tsanov, Kaloyan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pearson, Daniel S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roels, FrederikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spina, Catherine S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebright, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seligson, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Soysa, YvankaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cahan, PatrickUNSPECIFIEDorcid.org/0000-0003-3652-2540UNSPECIFIED
Theissen, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tu, Ho-ChouUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Han, AreumUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurek, Kyle C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
LaPier, Grace S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Osborne, Jihan K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ross, Samantha J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cesana, MarcellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collins, James J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berthold, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daley, George Q.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-269915
DOI: 10.1038/nature18632
Journal or Publication Title: Nature
Volume: 535
Number: 7611
Page Range: S. 246 - 264
Date: 2016
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-4687
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COMPARATIVE GENOMIC HYBRIDIZATION; COMPETITIVE ENDOGENOUS RNA; GENE-EXPRESSION; N-MYC; CANCER; TUMOR; LIN28B; CELLS; MIRNA; AMPLIFICATIONMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26991

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