Specific inhibition of hyperactive rRNA synthesis and protein translation was shown to be an effective way to suppress MYC/MYCN protein expression and neuroblastoma growth.
These data implicate tissue-specific enhancers in defining often highly tumor-specific 'MYC target gene signatures' and identify disruption of the MYCN enhancer regulatory axis as a promising therapeutic strategy in neuroblastoma.
These data suggest that epigenetic and posttranslational inhibition of MYC/MYCN-driven pathways may have significant clinical efficacy against neuroblastoma.
Our study implicates the role of BORIS/CTCFL in maintenance of stemness and in transition from mesenchymal to epithelial state in MYC amplified neuroblastoma IMR-32 cells.
MYC and MYCN control the expression of PD-L1 in neuroblastoma cells both <i>in vitro</i> and <i>in vivo</i> Consistently, abundance of PD-L1 transcript correlates with MYC expression in primary neuroblastoma.<b>Conclusions:</b> The combination of PD-L1 and HLA class I represents a novel prognostic biomarker for neuroblastoma.
This hypothesis-driven systems bioinformatics work offered novel insights into the PRC2-mediated tumor cell growth and differentiation in neuroblastoma, which may exert oncogenic effects together with MYC regulation.
Here, we found miR-1303 was upregulated in NB cells and tissues, miR-1303 overexpression promoted the proliferation of SH-SY5Y NB cell investigated by MTT assay, colony formation assay and anchorage-independent growth ability assay, while miR-1303 knockdown reduced this effect. mechanism analysis suggested glycogen synthase kinase 3 beta (GSK3β) and secreted frizzled-related protein 1 (SFRP1) were the target of miR-1303, luciferase assay revealed miR-1303 directly bound to the 3'UTR of GSK3β and SFRP1. miR-1303 increased expression of MYC and CyclinD1, and decreased the expression of p21 and p27, and further demonstrated miR-1303 promotes NB proliferation.
Amplification of the MYCN is the predominant marker for aggressive NB and correlates with poor prognosis, while c-MYC overexpression is a defining feature of MB subgroups inflected with aggressive biological behavior and increased likelihood of metastasis.
MYC coordinately regulates polyamine homeostasis as these essential cations support MYC functions, and drugs that antagonize polyamine sufficiency have synthetic-lethal interactions with MYCNeuroblastoma is a lethal tumor in which the MYC homologue MYCN, and ODC1, the rate-limiting enzyme in polyamine synthesis, are frequently deregulated so we tested optimized polyamine depletion regimens for activity against neuroblastoma.
Amplification of the MYCN oncogene, a member of the MYC family of transcriptional regulators, is one of the most powerful prognostic markers identified for poor outcome in neuroblastoma, the most common extracranial solid cancer in childhood.
Clinical data set analysis of MYCN, MYC and TWIST1 expression permits us to confirm that TWIST1 expression is upregulated in MYCN amplified neuroblastoma but also in a subset of neuroblastoma harboring high expression of MYCN or MYC without gene amplification.
TFs like MYC and PTEN having six types of adjacent nodes and other classes of TFs investigated really can help to demonstrate that TFs affect pathways through expressions of significant miRNAs involved in the pathogenesis of NB.
Taken together our data suggest that these small molecules may hold potential as effective therapeutic agents for the treatment of neuroblastoma and other MYC-driven cancers.
MYC has been shown to associate with DNA methyltransferases, thereby inducing transcriptional repression of target genes, which suggested that MYCN might play a similar mechanistic role in the hypermethylation of tumor suppressor genes in neuroblastoma.