title: Contradicting interplay between insulin-like growth factor-1 and miR-486-5p in primary NK cells and hepatoma cell lines with a contemporary inhibitory impact on HCC tumor progression.
abstract: In this study, an impaired natural killer (NK) cell cytolytic activity in 135 hepatocellular carcinoma (HCC) patients parallel to a reduced expression level of insulin-like growth factor (IGF)-1 in NK cells of HCC patients has been revealed. Ectopic expression of miR-486-5p, a direct upstream regulator of IGF-1, restored the endogenous level of IGF-1 in NK cells of HCC patients, thus augmenting its cytolytic activity against Huh7 cells in an opposite manner to the IGF-1 siRNAs. Unorthodoxly, over-expression of miR-486-5p in target hepatocytes resulted in the repression of IGF-1, suppression of Huh7 cells proliferation and viability in a similar pattern to the IGF-1 siRNAs. Therefore, this study highlights a potential role of IGF-1 in modulating cytolytic potential of NK cells of HCC patients. miR-486-5p acts in a cell-specific manner, differentially modulating IGF-1 expression in NK cells and their target hepatocytes with a contemporary inhibitory impact on HCC progression.
authors.affiliation: a Department of Pharmaceutical Biology , Faculty of Pharmacy and Biotechnology, German University in Cairo , Cairo , Egypt .
authors.forename: Rana Ahmed
authors.initials: RA
authors.lastname: Youness
authors.affiliation: a Department of Pharmaceutical Biology , Faculty of Pharmacy and Biotechnology, German University in Cairo , Cairo , Egypt .
authors.forename: Mai Atef
authors.initials: MA
authors.lastname: Rahmoon
authors.affiliation: b Department of Pharmacology and Toxicology , Faculty of Pharmacy and Biotechnology, German University in Cairo , Cairo , Egypt .
authors.forename: Reem Amr
authors.initials: RA
authors.lastname: Assal
authors.affiliation: c Department of Hepatology , National Liver Institute, Menoufiya University , Shebin El-Kom , Egypt .
authors.forename: Asmaa Ibrahim
authors.initials: AI
authors.lastname: Gomaa
authors.affiliation: d Department of Clinical Pathology , Ain Shams University , Cairo , Egypt , and.
authors.forename: Mohamed Tarif
authors.initials: MT
authors.lastname: Hamza
authors.affiliation: c Department of Hepatology , National Liver Institute, Menoufiya University , Shebin El-Kom , Egypt .
authors.forename: Imam
authors.initials: I
authors.lastname: Waked
authors.affiliation: b Department of Pharmacology and Toxicology , Faculty of Pharmacy and Biotechnology, German University in Cairo , Cairo , Egypt .
authors.forename: Hend Mohamed
authors.initials: HM
authors.lastname: El Tayebi
authors.affiliation: e Department of Biology , American University in Cairo , Cairo , Egypt.
authors.forename: Ahmed Ihab
authors.initials: AI
authors.lastname: Abdelaziz
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism
chemical_list: C556501:MIRN485 microRNA, human; D035683:MicroRNAs; D007334:Insulin-Like Growth Factor I
keywords: Insulin-like growth factor-1; NKG2A; NKG2D; hepatocellular carcinoma; immunotherapy; miR-486-5p; natural killer cells; perforins