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.

miR‐155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16‐bearing mice at the premetastatic stage

“…Our previous study found miR‐155 to be the most notably upregulated and miR‐205 the most notably downregulated microRNAs in melanoma, as compared with benign melanocytic tumours . Those data are in accordance with several studies reporting the role of miR‐155 as an oncogene and that of miR‐205‐5p as an oncosuppressor in various types of cancer . Taken together, these findings prompted us to further investigate the target genes of miR‐155 and miR‐205.…”

MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells

“…We previously reported that ectopic expression of miR-145 induces apoptosis through the downregulation of c-Myc and socs7 in bladder cancer cells [9–11]. We thus confirmed this effect by performing assays to evaluate apoptotic cell death in T24 and 253J B-V cells after the transfection of these cells with miR-145 or siR-KLF4.…”

Chemical Modification of the 3′-Dangling End of Small Interfering RNAs Such as siRNAs and miRNAs: The Development of miRNA Replacement Therapy

“…Because the modification shows enhanced nuclease-resistance and also binds a hydrophobic binding pocket of PAZ-domain of Ago2. Among the modified microRNAs, modified miR-205BP (4) significantly inhibited the growth of human melanoma cells [8] (Fig. 10).…”