| Literature DB >> 31287992 |
Patrick Sin-Chan1, Iqra Mumal2, Tannu Suwal2, Ben Ho1, Xiaolian Fan1, Irtisha Singh3, Yuchen Du4, Mei Lu1, Neilket Patel1, Jonathon Torchia5, Dean Popovski1, Maryam Fouladi6, Paul Guilhamon7, Jordan R Hansford8, Sarah Leary9, Lindsey M Hoffman10, Jean M Mulcahy Levy10, Alvaro Lassaletta11, Palma Solano-Paez12, Eloy Rivas13, Alyssa Reddy14, G Yancey Gillespie15, Nalin Gupta16, Timothy E Van Meter17, Hideo Nakamura18, Tai-Tong Wong19, Young-Shin Ra20, Seung-Ki Kim21, Luca Massimi22, Richard G Grundy23, Jason Fangusaro24, Donna Johnston25, Jennifer Chan26, Lucie Lafay-Cousin27, Eugene I Hwang28, Yin Wang29, Daniel Catchpoole30, Jean Michaud31, Benjamin Ellezam32, Ramya Ramanujachar33, Holly Lindsay4, Michael D Taylor34, Cynthia E Hawkins35, Eric Bouffet36, Nada Jabado37, Sheila K Singh38, Claudia L Kleinman37, Dalia Barsyte-Lovejoy39, Xiao-Nan Li40, Peter B Dirks34, Charles Y Lin3, Stephen C Mack4, Jeremy N Rich41, Annie Huang42.
Abstract
Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death.Entities:
Keywords: C19MC; ETMR; LIN28A; MYCN; brain tumor; cell-cycle; epigenetics; microRNA; super-enhancer; therapeutics
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Year: 2019 PMID： 31287992 DOI： 10.1016/j.ccell.2019.06.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743