The status of microRNA-21 expression and its clinical significance in human cutaneous malignant melanoma

Abstract

Dysregulation of microRNA-21 plays critical roles in tumor initiation and progression. The purpose of this study was to investigate the status of microRNA-21 expression in human cutaneous malignant melanoma and determine its clinical significance. TaqMan® real-time RT-PCR assay was performed to examine the expression of microRNA-21 in 10 cases of dysplastic nevi, 86 cases of primary cutaneous melanomas, 10 cases of melanoma metastases. The correlation of microRNA-21 expression with clinicopathological factors or prognosis of patients with cutaneous melanoma was statistically analyzed. Additionally, the effects of microRNA-21 expression on growth, apoptosis and chemo- or radiosensitivity of melanoma cells were also investigated by transfection of microRNA-21 inhibitor. We firstly showed that increased levels of microRNA-21 expression were shown from dysplastic nevi to primary cutaneous melanomas to melanoma metastases. Moreover, high miR-21 expression was found to be correlated with Breslow thickness and advanced clinical stage. Patients with high microRNA-21 expression showed shorter 5-year disease-free or overall survival than those with low microRNA-21 expression. Furthermore, multivariate regression analysis showed that the status of microRNA-21 expression was an independent prognostic factor for overall survival of patients. Antisense-mediated microRNA-21 inhibition could significantly suppress growth, increase apoptosis and enhance chemo- or radiosensitivity of human cutaneous melanoma cells by inducing the increased Bax/Bcl-2 ratio. Thus, the status of microRNA-21 might be an independent prognostic factor for patients with cutaneous melanoma, and microRNA-21 has the potential of being a novel molecular target for the treatment of human cutaneous melanoma.