Myc与Miz1的相互作用决定了髓母细胞瘤亚组的特征。
The Interaction of Myc with Miz1 Defines Medulloblastoma Subgroup Identity.
作者信息
Vo BaoHan T, Wolf Elmar, Kawauchi Daisuke, Gebhardt Anneli, Rehg Jerold E, Finkelstein David, Walz Susanne, Murphy Brian L, Youn Yong Ha, Han Young-Goo, Eilers Martin, Roussel Martine F
机构信息
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Theodor Boveri Institute, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
出版信息
Cancer Cell. 2016 Jan 11;29(1):5-16. doi: 10.1016/j.ccell.2015.12.003.
Four distinct subgroups of cerebellar medulloblastomas (MBs) differ in their histopathology, molecular profiles, and prognosis. c-Myc (Myc) or MycN overexpression in granule neuron progenitors (GNPs) induces Group 3 (G3) or Sonic Hedgehog (SHH) MBs, respectively. Differences in Myc and MycN transcriptional profiles depend, in part, on their interaction with Miz1, which binds strongly to Myc but not MycN, to target sites on chromatin. Myc suppresses ciliogenesis and reprograms the transcriptome of SHH-dependent GNPs through Miz1-dependent gene repression to maintain stemness. Genetic disruption of the Myc/Miz1 interaction inhibited G3 MB development. Target genes of Myc/Miz1 are repressed in human G3 MBs but not in other subgroups. Therefore, the Myc/Miz1 interaction is a defining hallmark of G3 MB development.
小脑髓母细胞瘤（MBs）的四个不同亚组在组织病理学、分子特征和预后方面存在差异。颗粒神经元前体细胞（GNPs）中c-Myc（Myc）或MycN的过表达分别诱导3组（G3）或 Sonic Hedgehog（SHH）MBs。Myc和MycN转录谱的差异部分取决于它们与Miz1的相互作用，Miz1与Myc紧密结合，但不与MycN结合，作用于染色质上的靶位点。Myc通过依赖Miz1的基因抑制作用抑制纤毛发生并重新编程SHH依赖的GNPs的转录组以维持干性。Myc/Miz1相互作用的基因破坏抑制了G3 MB的发展。Myc/Miz1的靶基因在人类G3 MBs中受到抑制，但在其他亚组中未受抑制。因此，Myc/Miz1相互作用是G3 MB发展的一个决定性标志。
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