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

• Published in: FEBS letters 2015-08, Vol.589 (17), p.2266-2273
• Main Authors: El-Ekiaby, Nada M., Mekky, Radwa Y., El Sobky, Shereen A., Elemam, Noha M., El-Sayed, Mohammed, Esmat, Gamal, Abdelaziz, Ahmed I.
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Adipocyte differentiation-related protein; ADRP; 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; HCV; Hepacivirus - genetics; Hepacivirus - physiology; Hepatitis C virus; Host-Pathogen Interactions - genetics; Humans; lipid droplet; Lipid droplets; Lipid Droplets - metabolism; Liver - metabolism; Liver - pathology; Liver - virology; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Liver Neoplasms - virology; Male; MicroRNAs - genetics; Middle Aged; miR-148a; miR-30a; oleic acid; Perilipin-3; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Viral - genetics; RNA, Viral - metabolism; Sequence Homology, Nucleic Acid; Tail interacting protein of 47kDa; TIP47; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2015.06.040

•TIP47 is upregulated in liver biopsies of HCV infected patients.•miR-148a and miR-30a are downregulated in liver biopsies of HCV infected patients.•miR-148a and miR-30a suppress TIP47 and decrease lipid droplets.•Forcing the expression of miR-148a and miR-30a decreases intracellular viral load. This study aimed at identifying potential microRNAs that modulate hepatic lipid droplets (LD) through targeting the Tail interacting protein of 47kDa (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.