title: Differential regulation of aggressive features in melanoma cells by members of the miR-17-92 complex.
abstract: The various roles of microRNAs (miRNAs) in controlling the phenotype of cancer cells are the focus of contemporary research efforts. We have recently shown that miR-17 directly targets the ADAR1 gene and thereby enhances melanoma cell aggressiveness. miR-17 and miR-20a belong to the miR-17/92 complex, and their mature forms are identical except for two non-seed nucleotides. Nevertheless, here we show that these two miRNAs carry markedly different effects on melanoma cells. A strong positive correlation was observed between the expression of miR-17 and miR-20a among various melanoma cultures. Luciferase assays showed that miR-17 but not miR-20a directly targets the 3' untranslated region of the ADAR1 gene. Ectopic expression of these miRNAs in melanoma cells differentially alters the expression of five exemplar TargetScan-predicted target genes: ADAR1, ITGB8, TGFBR2, MMP2 and VEGF-A. Whole-genome expression microarrays confirm a markedly differential effect on the transcriptome. Functionally, over-expression of miR-20a but not of miR-17 in melanoma cells inhibits net proliferation in vitro. The differential functional effect was observed following ectopic expression of the mature miRNA or of the pre-miRNA sequences. This suggests that the two non-seed nucleotides dictate target sequence recognition and overall functional relevance. These miRNAs are clearly not redundant in melanoma cell biology.
authors.affiliation: Sheba Medical Center, Ella Institute of Melanoma, Ramat Gan, Israel Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Greenberg
authors.affiliation: Sheba Medical Center, Ella Institute of Melanoma, Ramat Gan, Israel.
authors.forename: Steven
authors.initials: S
authors.lastname: Hajdu
authors.affiliation: Sheba Medical Center, Ella Institute of Melanoma, Ramat Gan, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Nemlich
authors.affiliation: Sheba Medical Center, Ella Institute of Melanoma, Ramat Gan, Israel Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Cohen
authors.affiliation: Sheba Medical Center, Ella Institute of Melanoma, Ramat Gan, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Itzhaki
authors.affiliation: Cancer Research Center, Ramat Gan, Israel.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Jacob-Hirsch
authors.affiliation: Sheba Medical Center, Ella Institute of Melanoma, Ramat Gan, Israel Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Besser
authors.affiliation: Sheba Medical Center, Ella Institute of Melanoma, Ramat Gan, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Schachter
authors.affiliation: Sheba Medical Center, Ella Institute of Melanoma, Ramat Gan, Israel Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Talpiot Medical Leadership Program, Sheba Medical Center, Ramat Gan, Israel markel@post.tau.ac.il.
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*
chemical_list: C524941:MIRN17 microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs
keywords: differential regulation; melanoma; miR-17; miR-17-92 cluster; miR-20a; proliferation