Year: 2015
Type: article
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.
Authors: John T. Powers, Kaloyan M. Tsanov, Daniel S. Pearson, Frederik Roels, Catherine S. Spina, Richard Ebright, Marc Seligson, Yvanka de Soysa, Patrick Cahan, Jessica Theißen, Ho-Chou Tu, Areum Han, Kyle C. Kurek, Grace S. LaPier, Jihan K. Osborne, Samantha J. Ross, Marcella Cesana, James J. Collins, Frank Berthold, George Q. Daley
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2605634095