@article{7b13e5045c7140cdbabcf16bbd2c0da7,
title = "Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma",
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.",
author = "Powers, {John T.} and Tsanov, {Kaloyan M.} and Pearson, {Daniel S.} and Frederik Roels and Spina, {Catherine S.} and Richard Ebright and Marc Seligson and {De Soysa}, Yvanka and Patrick Cahan and Jessica Thei{\ss}en and Tu, {Ho Chou} and Areum Han and Kurek, {Kyle C.} and Lapier, {Grace S.} and Osborne, {Jihan K.} and Ross, {Samantha J.} and Marcella Cesana and Collins, {James J.} and Frank Berthold and Daley, {George Q.}",
note = "Funding Information: G.Q.D. is supported by National Institutes of Health grant R01GM107536, Alex's Lemonade Stand Foundation, and the Ellison Medical Foundation. G.Q.D. is an affiliate member of the Broad Institute, and an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. J.T.P. was supported by Alex's Lemonade Stand Foundation. K.M.T. was supported as a Howard Hughes Medical Institute International Student Research Fellow and as a Herchel Smith Graduate Fellow. D.S.P. and R.E. were supported by award number T32GM007753 from the National Institute of General Medical Sciences. Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited, part of Springer Nature.",
year = "2016",
doi = "10.1038/nature18632",
language = "English (US)",
volume = "535",
pages = "246--251",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7611",
}