MicroRNA-485-5p represses melanoma cell invasion and proliferation by suppressing Frizzled7

Abstract MicroRNAs (miRNAs) have emerged as critical regulators for malignant melanoma development. miR-485-5p has been suggested as a tumor-suppressive miRNA in many types of human malignancies. However, the role of miR-485-5p in melanoma remains unknown. In this study, we aimed to explore the pote...

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Veröffentlicht in:Biomedicine & pharmacotherapy 2017-06, Vol.90, p.303-310
Hauptverfasser: Wu, Jiawen, Li, Jing, Ren, Jianwen, Zhang, Dingwei
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Sprache:eng
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Zusammenfassung:Abstract MicroRNAs (miRNAs) have emerged as critical regulators for malignant melanoma development. miR-485-5p has been suggested as a tumor-suppressive miRNA in many types of human malignancies. However, the role of miR-485-5p in melanoma remains unknown. In this study, we aimed to explore the potential role and underlying mechanism of miR-485-5p in the regulation of melanoma development. Here, we showed that miR-485-5p was significantly decreased in melanoma tissues and cell lines compared with their corresponding controls. Transwell invasion assay showed that miR-485-5p overexpression markedly inhibited melanoma cell invasion. WST-1 and cell cycle assays exhibited that miR-485-5p overexpression significantly suppressed melanoma cell proliferation. By contrast, miR-485-5p suppression promoted the invasion and proliferation of melanoma cells. Using bioinformatics analysis, we observed that miR-485-5p potentially targets the 3′-untranslated region (3′-UTR) of Frizzled7 (FZD7). Dual-luciferase assay confirmed the direct binding between miR-485-5p and FZD7 3′-UTR. Meanwhile, real-time quantitative polymerase chain reaction and Western blot analysis showed that miR-485-5p overexpression suppressed FZD7 expression, whereas miR-485-5p suppression resulted in the opposite effect. Moreover, miR-485-5p expression was observed to be inversely correlated with FZD7 mRNA expression in melanoma tissues. Further experiments showed that miR-485-5p regulated Wnt signaling. The restoration of FZD7 expression markedly reversed the antitumor effects induced by miR-485-5p overexpression in melanoma cells. Taken together, our study suggests that miR-485-5p represses melanoma cell invasion and proliferation by suppressing FZD7, indicating a new tumor-suppressive role for miR-485-5p in melanoma. The miR-485-5p/FZD7 axis may provide novel insights into understanding the molecular pathogenesis of melanoma and may be a promising therapeutic target for melanoma.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2017.03.064