Transcriptional Profile Tumor Evolution in Metastatic and Non Metastatic MYC driven HCC
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE243176 | GEO | 2024/08/06
REPOSITORIES: GEO
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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.
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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.
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Project description:Gene expression changes were examined in transgenic MYC-driven liver cancers at different time points as tumors formed and upon early regression. Time points evaluated include: Control (non-tumor bearing), Pre-tumor (mice were removed from doxyclycine in their diet to induce MYC oncogene expression for 4-5 weeks), Tumor (tumor nodules from mice that had been off of doxycycline for 8-9 weeks) and Early tumor regression (tumor-bearing mice were placed back on doxycycline for 72 hrs to inhibit MYC oncogene expresion). MYC-Driven Mouse Tumor Models are described in Schahaf, et al., Nature, 2004 and Goga, et al., Nature Medicine, 2007. 11 Total Samples: 3 Control, 4 Pre-Tumor, 4 Tumor, 4 Early Tumor Regression. Control = LAP-tTA transgenic mice. Others = TRE-MYC x LAP-tTA double transgenic mice (doxy off).
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