Aberrant MicroRNA Expression and Its Implications for Uveal Melanoma Metastasis

Kyra N Smit, Jiang Chang, Kasper Derks, Jolanda Vaarwater, Tom Brands, Rob M Verdijk, Erik A C Wiemer, Hanneke W Mensink, Joris Pothof, Annelies de Klein, Emine Kilic

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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.

Original languageEnglish
JournalCancers
Volume11
Issue number6
DOIs
Publication statusPublished - 12 Jun 2019

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    Smit, K. N., Chang, J., Derks, K., Vaarwater, J., Brands, T., Verdijk, R. M., Wiemer, E. A. C., Mensink, H. W., Pothof, J., de Klein, A., & Kilic, E. (2019). Aberrant MicroRNA Expression and Its Implications for Uveal Melanoma Metastasis. Cancers, 11(6). https://doi.org/10.3390/cancers11060815