Transcriptomic analyses of Myc-induced zebrafish liver cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE40745 | GEO | 2013/04/02
SECONDARY ACCESSION(S): PRJNA174800
REPOSITORIES: GEO
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Project description:To study the characteristics and mechanisms of Myc-induced zebrafish liver tumor, next-generation sequencing-based SAGE analyses were used to examine the transcriptomes of tumor and control samples. The results indicated that ribosome proteins were overwhelmingly up-regulated in the Myc-induced liver tumors. Cross-species analyses showed that the zebrafish Myc model correlated well with Myc transgenic mouse models for liver cancers. The Myc-induced zebrafish liver tumors also possessed molecular signatures highly similar to human hepatocellular carcinoma (HCC). Thus, our zebrafish model demonstrated the conserved role of Myc in promoting hepatocarcinogenesis in all vertebrate species. Transcriptome profiling of tumor samples (M+D+) and control samples (M-D-, M+D-, M-D+) were generated by deep sequencing, each in duplicates, using 3' RNA-SAGE on the SOLiD system.
2013-04-02 | E-GEOD-40745 | biostudies-arrayexpress
Project description:To compare the characteristics and mechanisms of Myc and xmrk induced zebrafish liver tumor, next generation sequencing-based SAGE analyses were used to examine the transcriptomes of tumor and control samples. The results indicated that relatively small overlaps of significantly deregulated genes and biological pathways among different zebrafish liver tumor models.Nevertheless, they all significantly correlate with advanced or very advanced human hepatocellular carcinoma (HCC). Molecular signature from each oncogene-induced zebrafish liver tumor correlated with only a small subset of human HCC samples, and they share conserved up-regulated pathways. A short list of commonly deregulated genes among different zebrafish liver tumors showed accordant deregulation in the majority of human HCCs, suggesting that they may serve as common diagnosis markers and therapeutic targets.Thus, these transgenic zebrafish models with well-defined oncogene-induced tumors are valuable tools for molecular classification of human HCCs and for understanding of molecular drivers in hepatocarcinogenesis in each human HCC subgroup. Transcriptome profiling of Myc tumor sample (X-M+D+) and control samples (X-M-D-, X-M+D-, X-M-D+), xmrk tumor sample (X+M-D+) and control samples (X-M-D-, X+M-D-, X-M-D+), were generated by deep sequencing, using 3' RNA-SAGE on SOLiD system
2013-12-17 | E-GEOD-53342 | biostudies-arrayexpress
Project description:To compare the characteristics and mechanisms of Myc and xmrk induced zebrafish liver tumor, next generation sequencing-based SAGE analyses were used to examine the transcriptomes of tumor and control samples. The results indicated that relatively small overlaps of significantly deregulated genes and biological pathways among different zebrafish liver tumor models.Nevertheless, they all significantly correlate with advanced or very advanced human hepatocellular carcinoma (HCC). Molecular signature from each oncogene-induced zebrafish liver tumor correlated with only a small subset of human HCC samples, and they share conserved up-regulated pathways. A short list of commonly deregulated genes among different zebrafish liver tumors showed accordant deregulation in the majority of human HCCs, suggesting that they may serve as common diagnosis markers and therapeutic targets.Thus, these transgenic zebrafish models with well-defined oncogene-induced tumors are valuable tools for molecular classification of human HCCs and for understanding of molecular drivers in hepatocarcinogenesis in each human HCC subgroup.
2013-12-17 | GSE53342 | GEO
Project description:transcriptome profiling of zebrafish liver tumors comparing with healthy liver tissues Zebrafish liver tumors were induced by exposure to 7,12-dimethylbenz(α)anthracene (DMBA). 5 zebrafish liver tumors and 6 healthy zebrafish livers were used to detect gene signatures in zebrafish liver tumors. A mixture of the 11 total RNA samples was used as the common reference.
2011-07-07 | E-GEOD-29307 | biostudies-arrayexpress
Project description:Transcriptomic analyses of Myc-induced zebrafish liver cancer
| PRJNA174800 | ENA
Project description:Activated mTORC2/AKT signaling plays a role in hepatocellular carcinoma (HCC). Research has shown that TSC/mTORC1 and FOXO1 are distinct downstream effectors of AKT signaling in liver regeneration and metabolism. However, the mechanisms by which these pathways mediate mTORC2/AKT activation in HCC are not yet fully understood. Amplification and activation of c-MYC is a key molecular event in HCC. In this study, we explored the roles of TSC/mTORC1 and FOXO1 as downstream effectors of mTORC2/AKT1 in c-MYC-induced hepatocarcinogenesis. Using various genetic approaches in mice, we found that manipulating the FOXO pathway had minimal impact on c-MYC-induced HCC. In contrast, loss of mTORC2 inhibited c-MYC-induced HCC, an effect that was completely reversed by ablating TSC2, which activated mTORC1. Additionally, we discovered that p70/RPS6 and 4EBP1/eIF4E act downstream of mTORC1, regulating distinct molecular pathways. Notably, the 4EBP1/eIF4E cascade is crucial for cell proliferation and glycolysis in c-MYC-induced HCC. We also identified centromere protein M (CENPM) as a downstream target of the TSC2/mTORC1 pathway in c-MYC-driven hepatocarcinogenesis, and its ablation entirely inhibited c-MYC-dependent HCC formation. Our findings demonstrate that the TSC/mTORC1/CENPM pathway, rather than the FOXO cascade, is the primary signaling pathway regulating c-MYC-driven hepatocarcinogenesis. Targeting CENPM holds therapeutic potential for treating c-MYC-driven HCC.
2024-09-15 | GSE275889 | GEO
Project description:Activated mTORC2/AKT signaling plays a role in hepatocellular carcinoma (HCC). Research has shown that TSC/mTORC1 and FOXO1 are distinct downstream effectors of AKT signaling in liver regeneration and metabolism. However, the mechanisms by which these pathways mediate mTORC2/AKT activation in HCC are not yet fully understood. Amplification and activation of c-MYC is a key molecular event in HCC. In this study, we explored the roles of TSC/mTORC1 and FOXO1 as downstream effectors of mTORC2/AKT1 in c-MYC-induced hepatocarcinogenesis. Using various genetic approaches in mice, we found that manipulating the FOXO pathway had minimal impact on c-MYC-induced HCC. In contrast, loss of mTORC2 inhibited c-MYC-induced HCC, an effect that was completely reversed by ablating TSC2, which activated mTORC1. Additionally, we discovered that p70/RPS6 and 4EBP1/eIF4E act downstream of mTORC1, regulating distinct molecular pathways. Notably, the 4EBP1/eIF4E cascade is crucial for cell proliferation and glycolysis in c-MYC-induced HCC. We also identified centromere protein M (CENPM) as a downstream target of the TSC2/mTORC1 pathway in c-MYC-driven hepatocarcinogenesis, and its ablation entirely inhibited c-MYC-dependent HCC formation. Our findings demonstrate that the TSC/mTORC1/CENPM pathway, rather than the FOXO cascade, is the primary signaling pathway regulating c-MYC-driven hepatocarcinogenesis. Targeting CENPM holds therapeutic potential for treating c-MYC-driven HCC.
2024-09-15 | GSE276215 | GEO
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:A complete understanding of molecular mechanisms that underlie cancer onset and progression could provide a basis to improve early diagnosis and more effective treatment. However, this is still a challenge in human, partly due to the difficulty of analyzing the early stages of the disease. In this context, genetically engineered mice represent a valuable alternative to model human carcinogenesis. Here, we studied cancer development in c-Myc/Tgfa transgenic mice that developed liver tumors which closely reproduce a subset of human hepatocellular carcinoma (HCC) with a poor prognosis. By using a functional genomics approach from early to late stages of HCC development, we demonstrated that hepatocarcinogenesis in c-Myc/Tgfa mice resulted from a progressive accumulation of transcriptional alterations due to an active hepatocyte proliferation in a chronic oxidative stress environment generated by a general metabolic disorder. One striking observation was the deregulation of numerous immune-related genes starting from an early stage of the disease. Particularly, we showed that activating ligands for natural killer (NK) cells were specifically induced in dysplastic hepatocytes which simultaneously lost the expression of MHC-I molecules. Besides this early mechanism of NK-mediated immune surveillance, we further reported a drastic decrease in hepatic NK cell population which may indeed contribute to the emergence and clonal expansion of progenitors for liver tumors. In conclusion, our study provided a detailed and comprehensive characterization of hepatocarcinogenesis in c-Myc/Tgfa transgenic mice and emphasized the critical role of the innate immune surveillance disruption at the early stages of liver cancer.
2011-09-28 | GSE25587 | GEO