Aberrant MicroRNA Expression and Its Implications for Uveal Melanoma Metastasis

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

doi:10.3390/cancers11060815

Cited by 33 publications

(41 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The study of Smit et al performed miRNA and mRNA expression profiling on 26 UM patient samples, to determine not only differentially expressed miRNA, but also their target genes and enriched cellular pathways involved in the progression of UM. The authors determined a set of 13 differentially expressed miRNAs, but in comparison with the data from this study and TCGA, some differences has been notified [20]. The discrepancies observed in those results are probably due to the use of different pipelines for next generation sequencing data analysis.…”

Section: Discussionmentioning

confidence: 92%

The Potential Role of Selected miRNA in Uveal Melanoma Primary Tumors as Early Biomarkers of Disease Progression

Wróblewska

Lach

Ustaszewski

et al. 2020

Genes

View full text Add to dashboard Cite

Uveal melanoma (UM) is the most common primary tumor of the eye diagnosed in adults, associated with a high risk of metastasis and thereby, poor prognosis. Among known risk factors for the development of metastatic disease is the loss of BAP1 expression and chromosome 3 monosomy in the primary tumor. However, the expression levels of specific micro RNAs (miRNA) in tumor tissue may also serve as a valuable marker for determining the risk of metastatic disease in patients with primary uveal melanoma. In our study, we analyzed the miRNA expression data of cases selected from The Cancer Genome Atlas study on uveal melanoma, and determined a panel of 15 miRNAs differentially expressed between patients with primary and metastatic disease. Next, 6 miRNAs were validated on a group of 46 tumor samples from primary and metastatic patients. We have shown, that expression of hsa-miR-592, hsa-miR-346, and hsa-miR-1247 was significantly increased, while hsa-miR-506 and hsa-miR-513c were decreased in the tumors of patients with metastatic disease. Hsa-miR-196b expression did not differ between the two subgroups, however, we showed significant correlation with BAP1 expression. Moreover, hsa-miR-592 also showed correlation with monosomy 3 tumors. Gene ontology analysis revealed involvement of those miRNAs with cellular processes mediating the metastatic process. Our results showed that miRNAs play an important role in the deregulation of several oncogenic pathways in UM and can, thereby, promote metastatic spread to distant organs. Moreover, differentially expressed miRNAs may be used as an interesting biomarker for the assessment of metastatic risk in uveal melanoma patients.

show abstract

Section: Discussionmentioning

confidence: 92%

The Potential Role of Selected miRNA in Uveal Melanoma Primary Tumors as Early Biomarkers of Disease Progression

Wróblewska

Lach

Ustaszewski

et al. 2020

Genes

View full text Add to dashboard Cite

show abstract

“…Aberrant microRNA (miRNA) expression, frequently observed in a myriad of cancers, is also reported in UM. The studies undertaken in UM include those investigating (a) the functional roles of specific miRNAs in cell lines and tumour samples [50,51] and (b) the prognostic and diagnostic use of miRNAs, individually and in networks, from not only tissue samples but also from plasma and circulating exosomes [52,53], as well as larger data-mining in silico studies often utilizing and extrapolating the power of The Cancer Genome Analysis (TCGA) study [54][55][56]. However, at present, there is no clear consensus as to which of the identified miRNAs should be targeted for use either as diagnostic biomarkers or as potential druggable targets.…”

Section: Introductionmentioning

confidence: 99%

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

Aughton

Kalirai

Coupland

2020

IJMS

View full text Add to dashboard Cite

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.

show abstract

“…Approximately 50% of patients with UVM develop metastatic disease (3), with the liver being the most common initial site of metastasis. Patients with metastatic disease are rarely candidates for curative surgery and generally have a poor prognosis; death often occurs within a few months of the development of metastases (4,5). Although the incidence rate of UVM is known to be influenced by a number of parameters, including demographic, geographic and, to a lesser extent, hereditary factors, little is known about the underlying mechanisms responsible for its initiation, progression or biological heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

Fatty acid‑binding protein 5 predicts poor prognosis in patients with uveal melanoma

Yang

Zhang

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Fatty acid-binding protein 5 (FABP5), which participates in mediating the biological properties of tumor cells, has been recognized in several neoplasms. The present study aims to investigate FABP5 transcriptional expression profiles, reveal its underlying biological interaction networks and define its prognostic value in uveal melanoma (UVM). A total of 80 patients with UVM and their RNA-sequence data, available from The Cancer Genome Atlas (TCGA) database, was analyzed. A differential transcriptional expression profile was obtained from TCGA and the Oncomine databases. The survival benefits were analyzed using the Kaplan-Meier method and log-rank test. The correlation between FABP5 expression and immune infiltration level was analyzed using the Tumor Immune Estimation Resource database. Functional enrichment analyses using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and signaling hallmarks were utilized to describe the biological process, molecular functions, cellular component and significantly involved pathways. The elevated transcriptional expression of FABP5 was significantly associated with shorter overall survival (OS) and worse progression-free survival (PFS) times in patients with UVM (P<0.001). Moreover, FABP5 expression was significantly and positively correlated with tumor purity and CD8 + T cells and was negatively correlated with the infiltrating levels of CD4 + T cells and neutrophils. Gene Set Enrichment Analysis was performed to obtain 100 significantly associated genes of FABP5 and FABP5 was found to be critical in several hallmark pathways, including allograft rejection, complement, interleukin-6/Janus kinase-STAT3 signaling, interferon γ response, inflammatory response and tumor necrosis factor α signaling via NFκB. The present study is the first to demonstrate that FABP5 expression was positively associated with progression-associated clinicopathological factors and poor prognosis in UVM, which suggests its likely function as an oncogene and prognostic marker in patients with UVM.

show abstract

Aberrant MicroRNA Expression and Its Implications for Uveal Melanoma Metastasis

Cited by 33 publications

References 62 publications

The Potential Role of Selected miRNA in Uveal Melanoma Primary Tumors as Early Biomarkers of Disease Progression

The Potential Role of Selected miRNA in Uveal Melanoma Primary Tumors as Early Biomarkers of Disease Progression

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

Fatty acid‑binding protein 5 predicts poor prognosis in patients with uveal melanoma

Contact Info

Product

Resources

About