title: Repression of miR-17-5p with elevated expression of E2F-1 and c-MYC in non-metastatic hepatocellular carcinoma and enhancement of cell growth upon reversing this expression pattern.
abstract: E2F-1, c-MYC, and miR-17-5p is a triad of two regulatory loops: a negative and a positive loop, where c-MYC induces the expression of E2F-1 that induces the expression of miR-17-5p which in turn reverses the expression of E2F-1 to close the loop. In this study, we investigated this triad for the first time in hepatocellular carcinoma (HCC), where miR-17-5p showed a significant down-regulation in 23 non-metastatic HCC biopsies compared to 10 healthy tissues; however, E2F-1 and c-MYC transcripts were markedly elevated. Forced over-expression of miR-17-5p in HuH-7 cells resulted in enhanced cell proliferation, growth, migration and clonogenicity with concomitant inhibition of E2F-1 and c-MYC transcripts expressions, while antagomirs of miR-17-5p reversed these events. In conclusion, this study revealed a unique pattern of expression for miR-17-5p in non-metastatic HCC patients in contrast to metastatic HCC patients. In addition we show that miR-17-5p is the key player among the triad that tumor growth and spread.
authors.affiliation: The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
authors.forename: H M
authors.initials: HM
authors.lastname: El Tayebi
authors.forename: K
authors.initials: K
authors.lastname: Omar
authors.forename: S
authors.initials: S
authors.lastname: Hegy
authors.forename: M
authors.initials: M
authors.lastname: El Maghrabi
authors.forename: M
authors.initials: M
authors.lastname: El Brolosy
authors.forename: K A
authors.initials: KA
authors.lastname: Hosny
authors.forename: G
authors.initials: G
authors.lastname: Esmat
authors.forename: A I
authors.initials: AI
authors.lastname: Abdelaziz
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002455:Cell Division; D002460:Cell Line; D050687:E2F1 Transcription Factor / Q000235:genetics*; D005260:Female; D016259:Genes, myc; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C524941:MIRN17 microRNA, human; D035683:MicroRNAs