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Expression data from pairwise non-tumor and tumor liver of -MYC and C-MYC/REG3A transgenic mice

ABSTRACT: Antimicrobial proteins of the REG3 family represent, like a wide variety of C-type lectins to which they belong, the first line of protection against infections and transformed cells. Their expression is inducible, particularly in response to inflammation, making their role in cancer biology less clear and controversial, as an immune-inflammation background may pre-exist or co-exist. We show that REG3A presents a suppressive role of REG3A in hepatocellular carcinoma (HCC) in a mouse models of HCC driven by c-MYC. By comparing the transcriptional profiles of liver tumors from MYC-REG3A-TG mice with those from MYC-TG mice, we found that MYC-REG3A tumors belonged to the S3 and G5 molecular subclasses of the human HCC classification proposed by Hoshida et al. and Boyault et al., respectively, subclasses that concentrate well-differentiated and CTNNB1-mutated HCCs. Tumors from MYC-TG mice exhibited features of S1 and G2/G3 subclasses. Results of the GSEA analysis indicate marked differential gene expression profiles. MYC-REG3A tumors and adjacent liver are enriched in metabolic pathways including bile acid, xenobiotic, and fatty acid metabolism, oxidative phosphorylation, and activation of Wnt/β-catenin signaling, whereas transcriptional reprogramming of MYC-TG mouse livers resulted in activation of cell cycle-, inflammation-, and glycolysis-related pathways as expected.

ORGANISM(S): Mus musculus

PROVIDER: GSE232521 | GEO | 2024/12/31

REPOSITORIES: GEO

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Project description:Medulloblastomas (MBs) are cerebellar tumors that can be classified into molecularly distinct subgroups that differ in pathology and prognosis. The mechanisms that underlie subgroup specification are largely unknown. While human SHH MBs express MYCN, Group3 (G3) MBs are associated with c-MYC (MYC) overexpression and often show metastasis that confers a poor prognosis. Although MYC proteins are thought to be functionally exchangeable, ectopic expression of Myc or N-myc in Trp53-/-;Cdkn2c-/- cerebellar granule neuron progenitors (GNPs) induces G3 and SHH MBs, respectively, demonstrating that each Myc protein has distinct biological properties. We now show that Myc and N-myc differ in their affinity to Miz1 and that Myc, but not N-myc, effectively recruits Miz1 to its target sites on chromatin. The interaction of Myc with Miz1 is required for the genesis of G3 MB. Myc suppresses ciliogenesis and âreprogramsâ the transcriptome of SHH-dependent GNPs to stem-like cells by repressing genes highly expressed in SHH MB via Miz1. Consistently, target genes of Myc/Miz1 are repressed in human G3 MBs but not in other MB subgroups. Collectively, the data show that the interaction of Myc with Miz1 is a defining hallmark of G3 MB development. In this study, we show that Myc and N-myc differ in their affinity for Miz1, and Myc/Miz1 interaction is required for Group3 medulloblastoma (MB). The gene expression profiles of these tumors were compared to our previously published Group3 MB model as well as SHH model of MB (Kawachi et al., 2012, Cancer Cell). Cerebellar granule neuron progenitors (GNPs) [dka220-222] from postnatal (P) 6 Math1-GFP;Trp53-/-;Cdkn2c-/-. For SHH medulloblastomas, [dka204-206] and [blm015-017 or dka050-dka051], spontaneous medulloblastomas from Cdkn2c-/-;Trp53Fl/Fl;Nestin-Cre (Kawachi et al., 2012, Cancer Cell) and Ptch1+/-;Cdkn2c-/- (Uziel et al., 2005, Genes Dev) were used, respectively. Myc- [dka201-203] and MycV394D (termed MycVD thereafter)- [bvo017-bvo023] tumors were from Trp53-/-;Cdkn2c-/- cerebella of P6-P7 pups. Myc/ÎPOZ tumors [bvo002-bvo006] were obtained from Trp5Fl/Fl;Miz1ÎPOZ/POZ;Nestin-Cre cerebella of P6-P7 pups.

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Expression data from pairwise non-tumor and tumor liver of -MYC and C-MYC/REG3A transgenic mice

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