title: 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 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.
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xi Wu Road, Xi'an, Shaanxi 710004, China. Electronic address: jiawenwujw@163.com.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xi Wu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xi Wu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xi Wu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D051157:Frizzled Receptors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C115810:FZD7 protein, human; D051157:Frizzled Receptors; C556501:MIRN485 microRNA, human; D035683:MicroRNAs
keywords: FZD7; Melanoma; MiR-485-5p; Wnt