Abstract
Uveal melanoma (UM) is the most frequently found primary intra-ocular tumor in adults. It is a highly aggressive cancer that causes metastasis-related mortality in up to half of the patients. Many independent studies have reported somatic genetic changes associated with high metastatic risk, such as monosomy of chromosome 3 and mutations in BAP1. Still, the mechanisms that drive metastatic spread are largely unknown. This study aimed to elucidate the potential role of microRNAs in the metastasis of UM. Using a next-generation sequencing approach in 26 UM samples we identified thirteen differentially expressed microRNAs between high-risk UM and low/intermediate-risk UM, including the known oncomirs microRNA-17-5p, microRNA-21-5p, and miR-151a-3p. Integration of the differentially expressed microRNAs with expression data of predicted target genes revealed 106 genes likely to be affected by aberrant microRNA expression. These genes were involved in pathways such as cell cycle regulation, EGF signaling and EIF2 signaling. Our findings demonstrate that aberrant microRNA expression in UM may affect the expression of genes in a variety of cancer-related pathways. This implies that some microRNAs can be responsible for UM metastasis and are promising potential targets for future treatment.
Highlights
Uveal melanoma (UM) is an aggressive cancer that arises from melanocytes located in the uveal tract of the eye
Twenty-six UM patients were enrolled in this study and grouped into three subtypes based on risk of developing metastasis (i.e. disease-free survival (DFS) and mutation status)
Since we aimed to identify miRNAs involved in the early metastasis of UM, we continued with thirteen miRNAs that were differentially expressed in the high-risk group, compared to the other two groups (Figure 2D)
Summary
Uveal melanoma (UM) is an aggressive cancer that arises from melanocytes located in the uveal tract of the eye. Treatment of primary tumors has a high success rate, up to half of the patients develop metastasis which often results in death within several months [1]. UM display chromosomal aberrations and genetic abnormalities that underlie both the development and metastasis of UM tumors. Most tumors carry a GNAQ or GNA11 mutation. These mutations are considered to be tumor-initiating mutations and do not increase the risk of metastasis [2,3,4]. UM patients can be stratified into three different metastatic risk groups; those who have a low-, intermediate-, or high-risk of developing metastasis [5]
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