Similar Datasets
Project description:To identify proteomic signatures associated with hepatocellular carcinoma driven by MYC overexpression, proteomics was performed on the LAP-tTA/tetO-MYC mouse conditional liver cancer model. Upon MYC activation, mice form liver cancer. Differential proteomics was performed in "MYC on" (MYC-HCC) mouse liver tumors versus mouse control normal liver tissue (where MYC was not overexpressed to drive tumorigenesis -- "MYC off").
2022-10-12 | PXD031478 | Pride
Project description:The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). However, MYC is considered undruggable to date. Here, we comprehensively identify genes essential for the survival of MYC-high but not MYC-low cells by performing a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen identifies novel MYC-synthetic lethal interactions, as well as most previously identified MYC-synthetic lethal genes. In particular, we found genes involved in nuclear to cytoplasmic transport to be MYC-synthetic lethal in HCC, and we show that many of these genes are transcriptionally upregulated in MYC-high murine HCC.
2023-10-30 | GSE205131 | GEO
Project description:Whole tissue RNA-seq analysis of mammary tumors from old (>12 months) and young (8-10 weeks) of mice after treatment with isotype, anti-CTLA4 or anti-PDL1 treatments.
2020-04-05 | GSE130472 | GEO
Project description:The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). However, MYC is considered undruggable to date. Here, we comprehensively identify genes essential for the survival of MYC-high but not MYC-low cells by performing a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen identifies novel MYC-synthetic lethal interactions, as well as most previously identified MYC-synthetic lethal genes. In particular, we found genes involved in nuclear to cytoplasmic transport to be MYC-synthetic lethal in HCC, and we show that many of these genes are transcriptionally upregulated in MYC-high murine HCC.
2023-10-30 | GSE205130 | GEO
Project description:The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). However, MYC is considered undruggable to date. Here, we comprehensively identify genes essential for the survival of MYC-high but not MYC-low cells by performing a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen identifies novel MYC-synthetic lethal interactions, as well as most previously identified MYC-synthetic lethal genes. In particular, we found genes involved in nuclear to cytoplasmic transport to be MYC-synthetic lethal in HCC, and we show that many of these genes are transcriptionally upregulated in MYC-high murine HCC.
2023-10-31 | GSE209798 | GEO
Project description:NanoString nCounter Human HCC expression analysis
| PRJNA488485 | ENA
Project description:Liver cancer is one of the leading causes of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the most common liver cancer, and limited therapeutic options are available. Here we discovered that urinary dimethylarginine, especially symmetric dimethylarginine (SDMA), was found to be increased in HCC in a MYC-dependent manner. Mechanistically, protein arginine methyltransferase 5 (Prmt5), which was highly induced in HCC, is a direct MYC target gene. Moreover, administration of GSK3326595, a PRMT5 inhibitor, to human MYC-overexpressing transgenic mice that spontaneously develop HCC, suppressed the growth of liver tumors. GSK3326595 exhibited anti-proliferative activity and enhanced anti-tumor immune response. Collectively, this study suggest that PRMT5 could be a new drug target for HCC treatment.
2021-05-10 | GSE154514 | GEO
Project description:We report a comparison of the genome-wide binding patterns of MYC and WDR5, and the effects of a mutation in MYC (WBM) that disrupt the MYC-WDR5 interaction. The experimental design included two distinct experimental strategies. For comparison of genome-wide binding patters of wild-type (WT) and WDR5 binding-deficient (WBM) MYC, HEK293 cells were engineered by retroviral transduction to express either FLAG-tagged WT-MYC, FLAG-tagged WBM-MYC, or an empty vector control ("vec") ChIP was performed on all samples using the anti-FLAG antibody, and co-precipitating DNAs subject to next-generation sequencing. Samples "2514-WPT-1_1", "2514-WPT-5_1" and "2514-WPT-13_1" are three independent biological replicates of ChIPs performed on the "vec" control cells (i.e., those not expressing any exogenous MYC). Samples "2514-WPT-2_1", "2514-WPT-6_1" and "2514-WPT-10_1" are three independent biological replicates of ChIPs performed on the WT-MYC expressing cells. "2514-WPT-3_1", "2514-WPT-7_1" and "2514-WPT-11_1" are three independent biological replicates of ChIPs performed on the WBM-MYC expressing cells. For comparison of these binding patterns with those of WDR5, we performed ChIP in HEK293 cells with either an antibody against WDR5, or with IgG (negative control). Samples "2514-WPT-23_1", "2514-WPT-25_1", and "2514-WPT-27_1" are independent biological replicates of ChIPs performed with the anti-WDR5 antibody. Samples "2514-WPT-24_1", "2514-WPT-26_1", and "2514-WPT-28_1" are independent biological replicates of ChIPs performed with the negative IgG control.
2015-03-30 | E-GEOD-60897 | biostudies-arrayexpress
Project description:Cancer cells associated with multiple survival strategies, and how cancer cells escape cell death under different conditions are still largely unknown. The Myc gene has been implicated in the pathogenesis of most types of human tumors. We show here that Eva1 (eva-1homolog A)/TMEM166 (transmembrane protein 166)/family with sequence similarity 176 (FAM176A) is upregulated by Myc/Max, however, overexpression of Eva1A induced mitotic catastrophe in hepatocellular carcinoma (HCC). Here, expression of Eva1A in HCC is suppressed by antisense long noncoding RNA, Eva1A-AS, that is induced also by Myc/Max, suggesting that Eva1A-AS expression supports HCC survival. Eva1A-AS is located within intron of Eva1A gene suppressed Eva1 expression by forming double stranded RNA with DiGeorge syndrome chromosomal region 8 (DGCR8). Depletion of Eva1A-AS in HepG2 cells upregulates Eva1A expression, and induced accumulation of lipid droplets and stopped cell proliferation. Furthermore, suppressed Eva1A expression levels are negatively correlated with differentiation grade in 371 primary HCCs. These data also suggest that EVA1A-AS may be useful target for a subset of HCCs.
2019-12-10 | GSE115139 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is an emerging risk factor of hepatocellular carcinoma (HCC). However, the mechanism and target therapy on NAFLD-HCC are still unclear. Here, we identify that the N6-methyladenosine (m6A) methyltransferase METTL3 promotes NAFLD-HCC. Hepatocyte-specific Mettl3 knockin exacerbated NAFLD-HCC formation while Mettl3 knockout exerted an opposite effect in mice. Single-cell RNA-seq revealed that METTL3 suppressed antitumor immune response by reducing infiltration of Gzmb+ and IFN-γ+ CD8+ T-cell, thereby facilitating immune escape. Mechanistically, METTL3 mediates SCAP mRNA m6A to promote its translation, leading to the activation of cholesterol biosynthesis. This enhanced secretion of cholesterol and cholesteryl esters, lipotoxins that impaired CD8+ T cell function in tumor microenvironment. Targeting of METTL3 by sgRNA, nanoparticle-siRNA, or pharmacological inhibitor (STM2457) in combination with anti-PD1 synergized to reinvigorate cytotoxic CD8+ T cells and mediate tumor regression. Together, METTL3 is a therapeutic target in NAFLD-HCC, especially in conjunction with immune checkpoint blockade (ICB) therapy.
2023-08-23 | GSE233807 | GEO