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

Acta Histochem. 2012 Oct;114(6):582-8. doi: 10.1016/j.acthis.2011.11.001. Epub 2011 Nov 29.

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.

MeSH terms

  • Apoptosis
  • Cell Survival
  • Flow Cytometry
  • Humans
  • Melanoma / diagnosis
  • Melanoma / genetics*
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Multivariate Analysis
  • Prognosis
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / genetics*
  • Survival Analysis
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Messenger