Role of the IncRNAs in malignant melanoma and their involvement in metastasis

Abstract

Malignant melanoma is an aggressive disease and its incidence is still rising. Despite available targeted therapies the prognosis of patients with advanced disease is relatively poor. Therefore, detailed understanding of the mechanisms that lead to melanoma development and characterization of the underlying molecular events associated with the outcome is essential for a more effective therapy. The molecular and cellular biology of melanomas involves a complex network of multiple factors interacting with different signaling pathways and disrupting the gene regulatory mechanisms. Recently, the long non-coding RNAs (IncRNAs) were identified as new transcriptional regulators modulating gene expression at various levels and playing an important role in diverse biological processes including carcinogenesis, tumor development and progression. Several IncRNAs have been shown to provide potential prognostic markers and represent novel therapeutic targets in different cancers. Aberrant expression of IncRNAs are frequently observed in various cancers including melanomas. However, studies investigating IncRNAs in malignant melanoma are limited and their potential or functional role in driving metastatic progression in particular is largely unknown. A recent report has revealed a mechanism by which the IncRNAs might mediate metastasis in melanoma. The study provided evidence that the IncRNA growth-arrest specific transcript 5 (GAS5) can modulate the metastatic capacity of melanoma cells by suppressing expression of the matrix metalloproteases MMP2 and MMP9. It was shown that knocking down GAS5 resulted in upregulation of the MMPs which may facilitate new therapeutic implications. In this article the current understanding on the role of IncRNAs and the associated functional mechanisms in melanoma pathogenesis and their involvement in promoting metastases are evaluated.