Integrated analysis of microRNA and mRNA expression profiles in HBx-expressing hepatic cells

World J Gastroenterol. 2017 Mar 14;23(10):1787-1795. doi: 10.3748/wjg.v23.i10.1787.

Abstract

Aim: To identify the miRNA-mRNA regulatory network in hepatitis B virus X (HBx)-expressing hepatic cells.

Methods: A stable HBx-expressing human liver cell line L02 was established. The mRNA and miRNA expression profiles of L02/HBx and L02/pcDNA liver cells were identified by RNA-sequencing analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed to investigate the function of candidate biomarkers, and the relationship between miRNA and mRNA was studied by network analysis.

Results: Compared with L02/pcDNA cells, 742 unregulated genes and 501 downregulated genes were determined as differentially expressed in L02/HBx cells. Gene ontology analysis suggested that the differentially expressed genes were relevant to different biological processes. Concurrently, 22 differential miRNAs were also determined in L02/HBx cells. Furthermore, integrated analysis of miRNA and mRNA expression profiles identified a core miRNA-mRNA regulatory network that is correlated with the carcinogenic role of HBx.

Conclusion: Collectively, the miRNA-mRNA network-based analysis could be useful to elucidate the potential role of HBx in liver cell malignant transformation and shed light on the underlying molecular mechanism and novel therapy targets for hepatocellular carcinoma.

Keywords: Hepatitis B virus X protein; Hepatocellular carcinoma; mRNA; miRNA; miRNA-mRNA network.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Cell Line
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Profiling
  • Hepatitis B virus
  • Hepatocytes / metabolism*
  • Hepatocytes / virology
  • Humans
  • Liver / cytology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • MicroRNAs / metabolism*
  • Molecular Targeted Therapy / methods
  • Neoplasm Invasiveness / genetics
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Trans-Activators / metabolism
  • Transfection
  • Viral Regulatory and Accessory Proteins

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Messenger
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein