lncRNAs-EZH2 interaction as promising therapeutic target in cutaneous melanoma

Abstract

Melanoma is the most lethal skin cancer with increasing incidence worldwide. Despite a great improvement of diagnostics and treatment of melanoma patients, this disease is still a serious clinical problem. Therefore, novel druggable targets are in focus of research. EZH2 is a component of the PRC2 protein complex that mediates epigenetic silencing of target genes. Several mutations activating EZH2 have been identified in melanoma, which contributes to aberrant gene silencing during tumor progression. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are molecular "address codes" for EZH2 silencing specificity, and targeting lncRNAs-EZH2 interaction may slow down the progression of many solid cancers, including melanoma. This review summarizes current knowledge regarding the involvement of lncRNAs in EZH2-mediated gene silencing in melanoma. The possibility of blocking lncRNAs-EZH2 interaction in melanoma as a novel therapeutic option and plausible controversies and drawbacks of this approach are also briefly discussed.

Keywords: EZH2; PRC2; epigenetics; immunotherapy; lncRNAs; melanoma; targeted therapy.