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Series GSE87578 Query DataSets for GSE87578
Status Public on Oct 28, 2016
Title Coordinated Activities of Multiple Myc-Dependent and Myc-Independent Biosynthetic Pathways in Hepatoblastoma
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Hepatoblastoma (HB) is associated with aberrant activation of the b-catenin and Hippo/YAP signaling pathways. Over-expression of mutant b-catenin and YAP in mice induces HBs that express high levels of c-Myc (Myc). In light of recent observations that Myc in unnecessary for long-term hepatocyte proliferation, we have now examined its role in HB pathogenesis using the above model. While Myc was found to be dispensable for in vivo HB initiation it was necessary to sustain rapid tumor growth. Gene expression profiling identified key molecular differences between myc+/+ (WT) and myc-/- (KO) hepatocytes and HBs that explain these behaviors. In HBs, these included both Myc-dependent and Myc-independent increases in families of transcripts encoding ribosomal proteins, non-structural factors affecting ribosome assembly and function and enzymes catalyzing glycolysis, lipid bio-synthesis and fatty acid b-oxidation. Myc-independent metabolic changes associated with HBs included dramatic reductions in mitochondrial mass and oxidative function and increases in ATP content and pyruvate dehydrogenase activity. Myc-dependent metabolic changes included higher levels of neutral lipid and acetyl-CoA in WT tumors. The latter correlated with higher histone H3 acetylation. Collectively, our results indicate that Myc’s role in HB pathogenesis is to impose mutually dependent changes in gene expression and metabolic re-programming that are unattainable in non-transformed cells and that cooperate to maximize tumor growth.
Overall design 4 individual sets each of Myc WT and KO hepatocytes, and 5 individual sets each of Myc WT and KO Hepatoblastoma
Contributor(s) Prochownik EV, Wang H
Citation(s) 27738108
Submission date Oct 03, 2016
Last update date May 15, 2019
Contact name Edward V Prochownik
Phone 412-692-6795
Organization name Children’s Hospital of Pittsburgh of UPMC
Department Division of Hematology/Oncology
Street address 4401 Penn Ave.
City Pittsburgh
State/province PA
ZIP/Postal code 15224
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (18)
GSM2334709 WT hepatocyte rep1
GSM2334710 WT hepatocyte rep2
GSM2334711 WT hepatocyte rep3
BioProject PRJNA345228
SRA SRP090770

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Supplementary file Size Download File type/resource
GSE87578_RAW.tar 30.6 Mb (http)(custom) TAR (of FPKM_TRACKING)
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Raw data are available in SRA
Processed data provided as supplementary file

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