title: MicroRNA-203 regulates melanosome transport and tyrosinase expression in melanoma cells by targeting kinesin superfamily protein 5b.
abstract: MicroRNA (miR)-203 is known to be downregulated and to act as an anti-oncomir in melanoma cells. At present, we found that exogenous miR-203 increased pigmentation and protein expression levels of the melanoma antigen recognized by T cells (Melan-As/MART1s) and/or tyrosinase (TYR) in the human melanoma cells tested. Inversely, treatment with an inhibitor of miR-203 downregulated the expression level of TYR. The target gene of miR-203 involved in the mechanism was kinesin superfamily protein 5b (kif5b), which was revealed by gene silencing using short interfering RNA and luciferase activity assay. Furthermore, immunocytochemistry showed obvious accumulation of melanosomes around nuclei of human melanoma Mewo cells transfected with miR-203 or siR-kif5b. Importantly, treatment with the miR-203 inhibitor, but not miR-203, exhibited effects on human epidermal melanocytes isolated from lightly pigmented adult skin similar to those on melanoma cells. In addition, the data indicated that exogenous miR-203 also negatively regulated the cAMP response element-binding protein 1 (CREB1)/microphthalmia-associated transcription factor (MITF)/Rab27a pathway, which is one of the main pathways active in melanoma cells. In conclusion, our data indicated that anti-oncogenic miR-203 had a pivotal role in melanoma through reducing melanosome transport and promoting melanogenesis by targeting kif5b and through negative regulation of the CREB1/MITF/Rab27a pathway.
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan. Electronic address: snoguchi@gifu-u.ac.jp.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan; Graduate School of Engineering, Gifu University, Gifu, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Kumazaki
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan; Graduate School of Engineering, Gifu University, Gifu, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yasui
authors.affiliation: Department of Veterinary Clinical Oncology, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mori
authors.affiliation: United Graduate School of Veterinary Medical Sciences, Gifu University, Gifu, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Yamada
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
mesh_terms: D001692:Biological Transport / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000078404:Epidermal Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020460:Melanosomes / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D024701:Myosin Type V / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C509805:KIF2A protein, human; C488101:KIF5B protein, human; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C077511:MYO5A protein, human; D014442:Monophenol Monooxygenase; D024701:Myosin Type V; D018995:Myosin Heavy Chains; D016547:Kinesins