MicroRNAs and Uveal Melanoma: Understanding the Diverse Role of These Small Molecular Regulators

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.

MiRNAs Correlate with HLA Expression in Uveal Melanoma: Both Up- and Downregulation Are Related to Monosomy 3

“…Robertson et al previously identified different miRNA clusters in UM which were associated with chromosome 3 status and also suggested that expression of some miRNAs might be related to the immune environment [11]. Similar to previous studies [11,[31][32][33][34][35], we observed a difference in miRs between low and high-risk UM.…”

“…One of the problems when looking at miRs is that different studies identify different miRs as being relevant: as stated in an extensive review by Aughton et al [33], it should be noted that many studies looked at miRNAs in UM and hardly ever were the same miRNAs reported as significantly associated with an increased metastatic risk in UM. As they stated, differences may be due to differences in tissue sampling, classifications or miRNA detection systems.…”

“…Several of the miRs have previously been associated with HLA expression or with inflammation. Aughton et al [33] compared the information from several papers on miRNAs in uveal melanoma and only found a few that had been reported in multiple papers. They described that miRNA that were associated with an increased metastatic risk could either be upregulated or downregulated.…”

“…In recent years, miRNAs have been identified as new players in tumorigenesis and metastases formation, and they have been associated with angiogenesis [24,25], the induction of epithelial-to-mesenchymal transition [26] and increased proliferation [27][28][29]. Several miRNAs have been identified to play a role in tumorigenesis of UM [30], and differences in miRNA expression occur between UM tumours with a low or high metastatic risk [31][32][33][34]. Smit reported that miRNAs were potential actors for the progression of metastasis in UM: 13 out of 423 mature miRNAs, which were expressed in UM samples, were differentially expressed between low, intermediate, and high-risk UM [35].…”

Proteomics Analysis: Inhibiting the Expression of P62 Protein by Chloroquine Combined with Dacarbazine Can Reduce the Malignant Progression of Uveal Melanoma

“…Uveal melanoma (UM) metastasis results from the malignant progression of the disease, as well as the beginning of an adverse prognosis [1], which has a close association with the change of its molecular biological characteristics [2,3,4,5]. In relation to target molecule therapies, the selection of key target molecules has attracted the attention of many researchers.…”