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.
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Authors | Shunsuke Noguchi, Junya Iwasaki, Minami Kumazaki, Takashi Mori, Kohji Maruo, Hiroki Sakai, Nami Yamada, Kazuyuki Shimada, Tomoki Naoe, Yukio Kitade, Yukihiro Akao |
Journal | Molecular therapy : the journal of the American Society of Gene Therapy
(Mol Ther)
Vol. 21
Issue 6
Pg. 1204-11
(Jun 2013)
ISSN: 1525-0024 [Electronic] United States |
PMID | 23629002
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BAX protein, human
- E2F1 Transcription Factor
- E2F1 protein, human
- MIRN205 microRNA, human
- MicroRNAs
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- bcl-2-Associated X Protein
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Topics |
- Animals
- Apoptosis
- Cell Line, Tumor
- Cell Proliferation
- Down-Regulation
- E2F1 Transcription Factor
(genetics, metabolism)
- Gene Expression Regulation, Neoplastic
- Genes, Tumor Suppressor
- Humans
- Injections, Intralesional
- Melanoma
(genetics, pathology)
- Mice
- Mice, Inbred BALB C
- MicroRNAs
(chemical synthesis, genetics)
- Real-Time Polymerase Chain Reaction
- Transfection
- Vascular Endothelial Growth Factor A
(genetics, metabolism)
- bcl-2-Associated X Protein
(genetics, metabolism)
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