Post-translational histone modifications such as acetylation and methylation can affect gene expression.,Histone acetylation is commonly associated with activation of gene expression whereas histone methylation is linked to either activation or repression of gene expression.,Depending on the site of histone modification, several histone marks can be present throughout the genome.,A combination of these histone marks can shape global chromatin architecture, and changes in patterns of marks can affect the transcriptomic landscape.,Alterations in several histone marks are associated with different types of cancers, and these alterations are distinct from marks found in original normal tissues.,Therefore, it is hypothesized that patterns of histone marks can change during the process of tumorigenesis.,This review focuses on histone methylation changes (both removal and addition of methyl groups) in malignant melanoma, a deadly skin cancer, and the implications of specific inhibitors of these modifications as a combinatorial therapeutic approach.
Effective management of melanoma depends heavily on early diagnosis.,When detected in early non-metastatic stages, melanoma is almost 100% curable by surgical resection, however when detected in late metastatic stages III and IV, 5-year survival rates drop to ~50% and 10-25%, respectively, due to limited efficacy of current treatment options.,This presents a pressing need to identify biomarkers that can detect patients at high risk of recurrence and progression to metastatic disease, which will allow for early intervention and survival benefit.,Accumulating evidence over the past few decades has highlighted the potential use of circulating molecular biomarkers for melanoma diagnosis and prognosis, including lactate dehydrogenase (LDH), S100 calcium-binding protein B (S100B) and circulating tumor DNA (ctDNA) fragments.,Since 2010, circulating microRNAs (miRNAs) have been increasingly recognised as more robust non-invasive biomarkers for melanoma due to their structural stability under the harsh conditions of the blood and different conditions of sample processing and isolation.,Several pre-analytical and analytical variables challenge the accurate quantification of relative miRNA levels between serum samples or plasma samples, leading to conflicting findings between studies on circulating miRNA biomarkers for melanoma.,In this review, we provide a critical summary of the circulating miRNA biomarkers for melanoma published to date.