MiR-431 is a prognostic marker and suppresses cell growth, migration and invasion by targeting NOTCH2 in melanoma.

Abstract

Aberrantly expressed microRNAs (miRNAs) are comprehensively involved in oncogenesis. A tumor-associated miRNA, miR-431, has been shown to play a functional effect in several tumors. However, the studies on the effects of miR-431 in melanoma were limited. The present study aimed to determine the levels of miR-431 in melanoma and to explore its clinical significance and potential function in melanoma carcinogenesis. Aberrant miRNAs in melanoma tissues were studied via miRNA microarray. MiR-431 expression in melanoma cell lines and carcinomas tissues were detected using RT-PCR. The clinical data were interpreted by the Chi-square test, Kaplan-Meier analysis, and multivariate analysis. The cell count kit (CCK-8) assay, flow cytometry wound healing, and transwell assays were used to assess the possible influence of miR-431 on tumor ability. The potential targets of miRNA-431 were predicted using an online tool and demonstrated by the use of dual luciferase assay and Western blot analysis. We observed that miR-431 expression was down-regulated in melanoma cells and tumor tissues, and reduced miR-431 levels were related to ulceration and tumor stage. The survival data revealed that melanoma patients with lower miR-431 suffered poorer overall survival. Multivariate analysis confirmed that miR-431 may be an independent prognostic marker for melanoma patients. Functional studies showed that miR-431 down-regulation inhibited melanoma growth and metastasis in vitro, while its overexpression has the opposite effects. Furthermore, we identified NOTCH2 as a direct target gene of miR-431 in melanoma cells. Besides, the restoration of NOTCH2 significantly reversed the inhibitory effects of miR-431 on melanoma cells growth and metastasis. Our observation suggested that miR-431 could be a new therapeutic target and prognostic marker of melanoma.