title: MicroRNA-206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D.
abstract: Expression profiling of microRNAs in melanoma lesional skin biopsies compared with normal donor skin biopsies, as well as melanoma cell lines compared with normal melanocytes, revealed that hsa-miR-206 was down-regulated in melanoma (-75.4-fold, P = 1.7 × 10(-4)). MiR-206 has been implicated in a large number of cancers, including breast, lung, colorectal, ovarian, and prostate cancers; however, its role in tumor development remains largely unknown, its biologic function is poorly characterized, and its targets affecting cancer cells are largely unknown. MiR-206 reduced growth and migration/invasion of multiple melanoma cell lines. Bioinformatics identified cell cycle genes CDK2, CDK4, Cyclin C, and Cyclin D1 as strong candidate targets. Western blots and 3'UTR reporter gene assays revealed that miR-206 inhibited translation of CDK4, Cyclin D1, and Cyclin C. Additionally, hsa-miR-206 transfection induced G1 arrest in multiple melanoma cell lines. These observations support hsa-miR-206 as a tumor suppressor in melanoma and identify Cyclin C, Cyclin D1, and CDK4 as miR-206 targets.
authors.affiliation: Medimmune, LLC, Gaithersburg, MD, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Georgantas
authors.forename: Katie
authors.initials: K
authors.lastname: Streicher
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Luo
authors.forename: Lydia
authors.initials: L
authors.lastname: Greenlees
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Philip
authors.initials: P
authors.lastname: Brohawn
authors.forename: Christopher
authors.initials: C
authors.lastname: Morehouse
authors.forename: Brandon W
authors.initials: BW
authors.lastname: Higgs
authors.forename: Laura
authors.initials: L
authors.lastname: Richman
authors.forename: Bahija
authors.initials: B
authors.lastname: Jallal
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yao
authors.forename: Koustubh
authors.initials: K
authors.lastname: Ranade
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001706:Biopsy; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D019295:Computational Biology; D056741:Cyclin D / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004789:Enzyme Activation; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D014176:Protein Biosynthesis; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D014019:Tissue Donors
chemical_list: D056741:Cyclin D; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D053148:Caspase 3; D053179:Caspase 7
keywords: G1 arrest; cell cycle; cell growth; invasion; microRNA; migration