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| Status |
Public on Oct 28, 2022 |
| Title |
Epigenetic aberrations of gene expression in a rat model of hepatocellular carcinoma |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Hepatocellular carcinoma (HCC) is mostly triggered by environmental and life-style factors and may involve epigenetic aberrations. However, a comprehensive documentation of the link between the dysregulated epigenome, transcriptome, and liver carcinogenesis is lacking. In the present study, Fischer-344 rats were fed a choline-deficient (CDAA, cancer group) or choline-sufficient (CSAA, healthy group) L-amino acid-defined diet. At the end of 52 weeks, transcriptomic alterations in livers of rats with HCC tumors and healthy livers were investigated by RNA sequencing. DNA methylation and gene expression were assessed by pyrosequencing and quantitative reverse-transcription PCR (qRT-PCR), respectively. We discovered 1,848 genes that were significantly differentially expressed in livers of rats with HCC tumors (CDAA) as compared with healthy livers (CSAA). Upregulated genes in the CDAA group were associated with cancer-related functions, whereas macronutrient metabolic processes were enriched by downregulated genes. Changes of highest magnitude were detected in numerous upregulated genes that govern key oncogenic signaling pathways, including Notch, Wnt, Hedgehog, and extracellular matrix degradation. We further detected perturbations in DNA methylating and demethylating enzymes, which was reflected in decreased global DNA methylation and increased global DNA hydroxymethylation. Four selected upregulated candidates, Mmp12, Jag1, Wnt4, and Smo, demonstrated promoter hypomethylation with the most profound decrease in Mmp12. MMP12 was also strongly overexpressed and hypomethylated in human HCC HepG2 cells as compared with primary hepatocytes, which coincided with binding of Ten-eleven translocation 1 (TET1). Our findings provide comprehensive evidence for gene expression changes and dysregulated epigenome in HCC pathogenesis, potentially revealing novel targets for HCC prevention/treatment.
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| Overall design |
Examination of transcriptome in livers of rats with hepatocellular carcinoma triggered by choline-deficient amino acid-defined diet (CDAA) as compared with livers of rats on healthy diet (choline-sufficient amino acid-defined diet, CSAA)
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| Contributor(s) |
Boycott C, Beetch M, Yang T, Lubecka K, Ma Y, Zhang J, Kendall LK, Ullmer M, Ramsey BS, Torregrosa-Allen S, Elzey BD, Cox A, Lanman NA, Hui A, Villanueva N, de Conti A, Huan T, Pogribny I, Stefanska B |
| Citation(s) |
35502615 |
| Submission date |
Mar 25, 2022 |
| Last update date |
Oct 28, 2022 |
| Contact name |
Barbara Stefanska |
| E-mail(s) |
barbara.stefanska@ubc.ca
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| Organization name |
The University of British Columbia
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| Department |
Land and Food Systems
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| Lab |
Stefanska Lab
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| Street address |
2205 East Mall
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| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V6T 1Z4 |
| Country |
Canada |
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| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA820003 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE199443_stefanska_rat_DEGs_csaaVScdaa.xlsx |
770.2 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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