PUBLICATION

Transcriptomic analyses of oncogenic hepatocytes reveal common and different molecular pathways of hepatocarcinogenesis in different developmental stages and genders in krasG12V transgenic zebrafish

Authors
Huo, X., Li, H., Li, Z., Yan, C., Mathavan, S., Liu, J., Gong, Z.
ID
ZDB-PUB-190212-1
Date
2019
Source
Biochemical and Biophysical Research Communications   510(4): 558-564 (Journal)
Registered Authors
Gong, Zhiyuan, Li, Zhen, Mathavan, S.
Keywords
HCC (hepatocellular carcinoma), Hepatocytes, Kras, RNA-Seq, Zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified/genetics
  • Carcinogenesis/genetics*
  • Carcinogenesis/pathology
  • Carcinoma, Hepatocellular/genetics*
  • Carcinoma, Hepatocellular/pathology
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling
  • Hepatocytes/metabolism
  • Hepatocytes/pathology*
  • Liver Neoplasms/genetics*
  • Liver Neoplasms/pathology
  • Male
  • Point Mutation
  • Proto-Oncogene Proteins p21(ras)/genetics*
  • Transcriptome
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
PubMed
30739784 Full text @ Biochem. Biophys. Res. Commun.
Abstract
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is mainly due to genetic changes in hepatocytes. However, molecular expression in hepatocytes during hepatocarcinogenesis has not been characterized. In this study, using an inducible kras transgenic zebrafish models for HCC, transcriptomic profiles of oncogenic hepatocytes from larvae, male and female adult fish following a brief induction of oncogenic kras were investigated. We found that oncogenic hepatocytes from all the three sources possess most of the cancer hallmarks at molecular level, including Sustaining proliferative signaling, Evading growth suppressors, Resisting cell death, Avoiding immune destruction, Inflammation, Reprogramming of energy metabolism, Angiogenesis, and Activating invasion and metastasis, suggesting the malignant transformation at molecular level could occur at the early stage of hepatocarcinogensis and can be captured in hepatocytes. However, each group of oncogenic hepatocytes also had their own characteristics. Larval oncogenic hepatocytes have cancer stem cell features. Female oncogenic hepatocytes showed resemblance to a mild human HCC subtype while male oncogenic hepatocytes resembled a severe HCC subtype, consistent with the observed sex disparity of HCC in both zebrafish and human. Finally, the two adult groups were more similar to each other than to the larval group, indicating an overwhelming effect of development over the gender.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping