Epigenetic aberrations of gene expression in a rat model of hepatocellular carcinoma.
Animals
Humans
Rats
Amino Acids
/ genetics
Carcinoma, Hepatocellular
/ pathology
Choline
DNA
/ metabolism
DNA Methylation
Epigenesis, Genetic
Gene Expression
Liver Neoplasms
/ metabolism
Matrix Metalloproteinase 12
/ genetics
Mixed Function Oxygenases
/ genetics
Proto-Oncogene Proteins
/ genetics
Rats, Inbred F344
DNA methylation
Transcriptomics
liver cancer
oncogenes
Journal
Epigenetics
ISSN: 1559-2308
Titre abrégé: Epigenetics
Pays: United States
ID NLM: 101265293
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
pubmed:
4
5
2022
medline:
21
10
2022
entrez:
3
5
2022
Statut:
ppublish
Résumé
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 tumours 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 tumours (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 signalling 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,
Identifiants
pubmed: 35502615
doi: 10.1080/15592294.2022.2069386
pmc: PMC9586690
doi:
Substances chimiques
Amino Acids
0
Choline
N91BDP6H0X
DNA
9007-49-2
Matrix Metalloproteinase 12
EC 3.4.24.65
Mixed Function Oxygenases
EC 1.-
Proto-Oncogene Proteins
0
TET1 protein, human
EC 1.-
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1513-1534Subventions
Organisme : NCI NIH HHS
ID : P30 CA023168
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA082709
Pays : United States
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