Epigenetic harnessing of HCV via modulating the lipid droplet-protein, TIP47, in HCV cell models

FEBS Lett. 2015 Aug 4;589(17):2266-73. doi: 10.1016/j.febslet.2015.06.040. Epub 2015 Jul 10.

Abstract

This study aimed at identifying potential microRNAs that modulate hepatic lipid droplets (LD) through targeting the Tail interacting protein of 47 kDa (TIP47) in HCV infection. Bioinformatics analysis revealed that miR-148a and miR-30a potentially target TIP47. Expression profiling showed that both microRNAs were downregulated, while TIP47 was upregulated in liver biopsies of HCV-infected patients. Forcing the expression of both microRNAs in JFH-I infected, oleic acid-treated Huh7 cells, significantly suppressed TIP47 expression and reduced cellular LDs with marked decrease in viral RNA. This study shows that miR-148a and miR-30a, regulate TIP47 expression and LDs in HCV infected cells.

Keywords: HCV; Lipid droplets; Tail interacting protein of 47kDa; miR-148a; miR-30a.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Aged
  • Base Sequence
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Cell Line, Tumor
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hepacivirus / genetics*
  • Hepacivirus / physiology
  • Host-Pathogen Interactions / genetics
  • Humans
  • Lipid Droplets / metabolism*
  • Liver / metabolism
  • Liver / pathology
  • Liver / virology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Perilipin-3
  • RNA Interference
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Vesicular Transport Proteins / genetics*
  • Vesicular Transport Proteins / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN148 microRNA, human
  • MIRN30b microRNA, human
  • MicroRNAs
  • PLIN3 protein, human
  • Perilipin-3
  • RNA, Viral
  • Vesicular Transport Proteins