Project description:The mechanisms underlying hepatoblastoma are not well defined. To address this, we generated transcriptomic profiles of normal, background, and hepatoblastoma liver samples from patients aged 0.01 months to 6 years, using RNA-sequencing. Hepatoblasoma was histologically confirmed. Here we focus on the elevation of stem cell markers and the loss of tumor suppressor proteins leading to the development of hepatoblastoma in very young children.
Project description:We performed a genome-wide analysis of lncRNA expression in hepatoblastoma tissues to identify novel targets for further study of hepatoblastoma.We found that 2736 lncRNAs were differentially expressed in hepatoblastoma tissues. The genome-wide analysis of lncRNA expression in these tissues was performed using a 4 M-CM-^W 180K lncRNA microarray and Sureprint G3 Human lncRNA Chips.Quantitative RT-PCR (qRT-PCR) was performed to confirm these results.
Project description:We performed a genome-wide analysis of lncRNA expression in hepatoblastoma tissues to identify novel targets for further study of hepatoblastoma.We found that 2736 lncRNAs were differentially expressed in hepatoblastoma tissues.
Project description:We identified mebendazole as a drug to circumvent chemoresistance in hepatoblastoma cell lines that are resistant to cisplatin. In order to identify the mechanistic basis of mebendazole function, we performed gene expression analysis of three mebendazole-treated hepatoblastoma cell lines.
Project description:The effects of GATA4 silencing on global gene expression in HUH6 hepatoblastoma cells was analyzed. Using microarray analysis we identified a set of genes that are downregulated or upregulated following silencing of GATA4 in HUH6 cell line.
Project description:Purpose: Despite an overall good outcome of hepatoblastoma patients, prognosis is still poor if associated with metastatic disease. Transcriptomic profiling enables a global view on deregulated cellular pathways. The goal of this study was to compare RNAseq data of metastasized and non-metastasized specimens to identify new molecular players for high-risk hepatoblastoma patients.
Project description:Lack of relevant disease animal models and cell lines hampers our understanding of hepatoblastoma and identification of therapeutic targets. We report a liver-specific MYC-driven hepatoblastoma murine model that faithfully recapitulates the pathological features of mixed fetal and embryonic hepatoblastoma, with transcriptomics resembling the high-risk gene signatures of human disease. Single-cell RNA-sequencing (scRNA-seq) and spatiotranscriptomics identify a subpopulation of hepatoblastoma cells with high levels of adult hemoglobin genes. After deriving a cell line from the mouse model, we mapped the cancer dependency genes using CRISPR-Cas9 and identified druggable targets shared with human hepatoblastoma (i.e., CDK7, CDK9, PRMT1, PRMT5). Our screen also discovered oncogenes and tumor suppressive genes in hepatoblastoma that engage multiple cancer signaling pathways. Chemotherapy is the mainstay of human hepatoblastoma. Genetic map of doxorubicin response by CRISPR-Cas9 identified modifiers whose loss-of-function synergizes (PRKDC) and antagonizes (Polycomb repressive complex 2) the effect of chemotherapy. Combination of PRKDC inhibitor and chemotherapy greatly enhances therapeutic efficacy. Our studies have provided useful disease models and potential therapeutic targets of hepatoblastoma.
Project description:Modeling Hepatoblastoma: Identification of Distinct Tumor Cell Populations and Key Genetic Mechanisms through Single Cell Sequencing (bulk)
