title: MicroRNA-486-5p enhances hepatocellular carcinoma tumor suppression through repression of IGF-1R and its downstream mTOR, STAT3 and c-Myc.
abstract: The insulin-like growth factor (IGF)-axis has been paradigmatically involved in hepatocellular carcinoma (HCC) tumor initiation, progression and drug resistance. Consequently, members of the IGF-axis and most importantly, IGF-1 receptor (IGF-1R) have been considered as intriguing targets for HCC therapy. Few miRNAs have been recently reported to be associated with IGF-1R regulation. The present study aimed to investigate the role of microRNA (miRNA/miR)-486-5p in the regulation of IGF-1R and its downstream signaling cascades. miR-486-5p was markedly downregulated in hepatitis C virus-induced HCC tissues and Huh-7 cells. Forcing the expression of miR-486-5p in Huh-7 cells resulted in the repression of IGF-1R, mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3) and c-Myc mRNA levels. Ectopic expression of miR-486-5p in Huh-7 cells markedly repressed cellular viability, proliferation, migration and clonogenicity in a similar pattern to IGF-1R small interfering RNAs, and were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, BrdU incorporation, wound healing and colony forming assays, respectively. Overall, the study findings demonstrated that miR-486-5p acts as a tumor suppressor in HCC through the repression of essential members of the IGF-axis, including IGF-1R and its downstream mediators mTOR, STAT3 and c-Myc.
authors.affiliation: Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, New Cairo City, Cairo 11835, Egypt.
authors.forename: Rana Ahmed
authors.initials: RA
authors.lastname: Youness
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, New Cairo City, Cairo 11835, Egypt.
authors.forename: Hend Mohamed
authors.initials: HM
authors.lastname: El-Tayebi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, New Cairo City, Cairo 11835, Egypt.
authors.forename: Reem Amr
authors.initials: RA
authors.lastname: Assal
authors.affiliation: Department of General Surgery, Faculty of Medicine, Cairo University, Giza 12613, Egypt.
authors.forename: Karim
authors.initials: K
authors.lastname: Hosny
authors.affiliation: Department of Endemic Medicine and Hepatology, Cairo University, Giza 12613, Egypt.
authors.forename: Gamal
authors.initials: G
authors.lastname: Esmat
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, New Cairo City, Cairo 11835, Egypt.
authors.forename: Ahmed Ihab
authors.initials: AI
authors.lastname: Abdelaziz
keywords: HCC; IGF-1R; STAT3; c-Myc; mTOR; microRNA-486-5p