MiR-124 inhibits proliferation, migration and invasion of malignant melanoma cells via targeting versican.

Abstract

MicroRNA (miR)-124 has been implicated in malignant melanoma (MM). However, the detailed regulatory mechanism of miR-124 in the malignant phenotypes of MM cells has remained largely elusive. A total of 68 pairs of MM tissues and adjacent tissues were collected. Reverse-transcription quantitative polymerase chain reaction was used to examine the mRNA expression of versican as well as the expression of miR-124, and the protein expression of versican was assessed by western blot analysis. MTT, wound healing and Transwell assays were used to determine cell proliferation, migration and invasion, respectively. A bioinformatics analysis and a luciferase reporter assay were used to confirm the targeting association between miR-124 and versican. miR-124 was significantly downregulated in MM tissues compared with that in adjacent non-tumorous tissues, and decreased expression of miR-124 was associated with increased tumor thickness, advanced clinical stage and node metastasis of MM. Furthermore, the expression levels of miR-124 were also reduced in MM cell lines compared with normal human skin HACAT cells. Forced overexpression of miR-124 caused a significant reduction in the proliferation, migration and invasion of MM A375 cells. Versican was significantly upregulated in MM tissues and cell lines, and was identified as a novel target of miR-124 in A375 cells using a luciferase reporter gene assay, and miR-124 was revealed to negatively regulate the protein expression of versican in A375 cells. Overexpression of versican impaired the suppressive effects of miR-124 on the proliferation, migration and invasion of A375 cells. In conclusion, miR-124 inhibited the malignant phenotypes of MM cells at least partly via inhibition of versican. Therefore, the miR-124/versican axis may be used as a promising therapeutic target for inhibiting MM growth and metastasis.