title: Chemically modified synthetic microRNA-205 inhibits the growth of melanoma cells in vitro and in vivo.
abstract: microRNA (miR)-205 is downregulated and acts as a tumor suppressor in human melanoma cells. Previously, for clinical application, we added aromatic benzene-pyridine (BP-type) analogs to the 3'-overhang region of the RNA-strand and changed the sequences of the passenger strand in the miR-143 duplex. Here, we demonstrated the antitumor effect in vitro and in vivo of miR-205 that was also chemically modified by BP and had altered passenger sequence. In in vitro experiments, transfection with the synthetic miR-205 (miR-205BP/S3) significantly inhibited the growth of human melanoma cells. Exogenous miR-205BP/S3 suppressed the protein expression levels of E2F1 and VEGF, which are validated targets of miR-205-5p, and BCL2, a transcribed molecule of E2F1, as did Pre-miR-205, used as a miR-205 mimic having the wild-type sequence. On the basis of the results of a luciferase activity assay, miR-205BP/S3 directly targeted E2F1, as did Pre-miR-205. However, miR-205BP/S3 was much more resistant to RNase than Pre-miR-205 in fetal bovine serum and to RNase in mice xenografted with human melanoma tissues. In addition, the intratumoral injection of miR-205BP/S3 exhibited a significant antitumor effect compared with the case of control miRNA or Pre-miR-205 in human melanoma cell-xenografted mice. These findings indicate that miR-205BP/S3 is a possible promising therapeutic modality for melanoma.
authors: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan. snoguchi@gifu-u.ac.jp
authors: Shunsuke
authors: S
authors: Noguchi
authors: Junya
authors: J
authors: Iwasaki
authors: Minami
authors: M
authors: Kumazaki
authors: Takashi
authors: T
authors: Mori
authors: Kohji
authors: K
authors: Maruo
authors: Hiroki
authors: H
authors: Sakai
authors: Nami
authors: N
authors: Yamada
authors: Kazuyuki
authors: K
authors: Shimada
authors: Tomoki
authors: T
authors: Naoe
authors: Yukio
authors: Y
authors: Kitade
authors: Yukihiro
authors: Y
authors: Akao
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D015552:Injections, Intralesional; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000138:chemical synthesis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D050687:E2F1 Transcription Factor; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C493753:E2F1 protein, human; C534425:MIR205, human; C467484:VEGFA protein, human
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