Abstract
Uveal melanoma (UM) is a rare tumour of the eye, characterised by a high propensity to metastasise in half of all patients, most frequently to the liver. Although there are effective treatment options for the primary tumour, once metastasis has occurred prognosis is poor, with overall survival limited to months. Currently, there are no effective treatments for metastatic UM, despite the tumour having a well-defined signalling pathway to which many therapies have been directed. In an effort to develop novel treatment approaches, understanding the role of other signalling molecules, such as microRNAs, is fundamental. MicroRNAs (miRNAs) are small non-coding RNA molecules involved in posttranscriptional gene regulation, resulting in reduced target gene expression and subsequent protein translation. In UM, several dysregulated miRNAs have been proposed to play a functional role in disease progression, whereas others have been put forward as clinical biomarkers of high-risk disease following isolation from blood, plasma and exosomes. Most recently, analyses of large datasets have identified promising prognostic miRNA signatures and panels. This review navigates the plethora of aberrant miRNAs disclosed so far in UM, and maps these to signalling pathways, which could be targeted in future therapies for the disseminated disease.
Highlights
Uveal melanoma (UM), the most common primary intraocular tumour, is a rare disease, affecting approximately 4–6 adults per million annually [1,2]
This review explores aberrant miRNA expression in UM and maps these to signalling pathways that appear to regulate UM growth and could be exploited as future drug targets
Differences in study design, tissue sample classifications and miRNA detection systems may all contribute to the differences in miRNAs reported as significantly associated with an increased metastatic risk in UM
Summary
Uveal melanoma (UM), the most common primary intraocular tumour, is a rare disease, affecting approximately 4–6 adults per million annually [1,2]. A TCGA-UM study, which analysed 80 primary UM samples, identified four main miRNA clusters that were clearly associated with chromosome 3 status, metastatic risk and corresponding DNA methylation profile [56]. Differences in study design, tissue sample classifications and miRNA detection systems (microarray vs RNA-Seq) may all contribute to the differences in miRNAs reported as significantly associated with an increased metastatic risk in UM. This lack of commonality between studies emphasises the need for functional validation of any proposed miRNAs as biomarkers in UM moving forward
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