Differential network analysis depicts regulatory mechanisms for hepatocellular carcinoma from diverse backgrounds

Future Oncol. 2019 Dec;15(34):3917-3934. doi: 10.2217/fon-2019-0275. Epub 2019 Nov 15.

Abstract

Aim: To elucidate the integrative combinational gene regulatory network landscape of hepatocellular carcinoma (HCC) molecular carcinogenesis from diverse background. Materials & methods: Modified gene regulatory network analysis was used to prioritize differentially regulated genes and links. Integrative comparisons using bioinformatics methods were applied to identify potential critical molecules and pathways in HCC with different backgrounds. Results: E2F1 with its surrounding regulatory links were identified to play different key roles in the HCC risk factor dysregulation mechanisms. Hsa-mir-19a was identified as showed different effects in the three HCC differential regulation networks, and showed vital regulatory role in HBV-related HCC. Conclusion: We describe in detail the regulatory networks involved in HCC with different backgrounds. E2F1 may serve as a universal target for HCC treatment.

Keywords: E2F1; TCGA database; differential regulation network analysis; etiological factor; hepatocellular carcinoma; hsa-mir-19a.

MeSH terms

  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / virology
  • Computational Biology
  • Datasets as Topic
  • Disease-Free Survival
  • E2F1 Transcription Factor / antagonists & inhibitors
  • E2F1 Transcription Factor / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Regulatory Networks*
  • Hepacivirus / isolation & purification
  • Hepacivirus / pathogenicity
  • Hepatitis B virus / isolation & purification
  • Hepatitis B virus / pathogenicity
  • Humans
  • Kaplan-Meier Estimate
  • Liver / pathology
  • Liver / virology
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / virology
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Prognosis

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • MIRN19A microRNA, human
  • MicroRNAs