Differences in microRNA expression between melanoma and healthy adjacent skin

Abstract

BackgroundThe tumor microenvironment is composed of cancer-associated fibroblasts, tumor-associated macrophages, endothelial cells, immune cells, signaling molecules and extracellular matrix structures, which closelycommunicate with the tumor via multiple mechanisms. MicroRNAs are paracrine regulators that provide a direct interaction between the microenvironment and cancer cells. In the presentstudy, we aimed to identify the microRNA expression profile in melanoma compared with thatin healthy adjacent skin, with a further assessment of altered microRNA signaling pathways and target genes.MethodsFormalin-fixed paraffin-embedded (FFPE) melanoma tissue samples were separated by dissection into tumor and surrounding health tissue fragments. MicroRNA expression profiles were obtained by microarray using Gene Atlas Microarray System (Affymetrix, California, USA). To confirm microarray results real-time PCR was carried out. Bioinformatic analysis was performed using the DIANA-miRPath v.3.0 database. Target genes for miR-146a-5p were determined using three algorithms: TargetScan 7.0, miRWalk 2.0 and miRTarBase v.4.5.ResultsA microarray profiling revealed 143 microRNAs asdifferent in tumor versus adjacent tissues. Expression level of hsa-miR-146a-5p showedto be higher in melanoma cells as compared to thehealthy adjacent skin. The bioinformatic study has determined several signaling cascades associated with miR-146a-5p:Toll-like receptor pathway, NF-κB pathway, ErB pathway, and measles signaling pathway. The 38 target genes have been shown for miR-146a-5p of which NRAS gene is known asone of the most frequent mutated in melanoma.ConclusionsElucidation of the role of miR-146-a-5p in complex interactions between the tumor and the cells of healthy adjacent skin is necessary for our understanding of the mechanisms oftumor progression. Significant differences found between cancer cells and adjacent tissues in microRNA expression profile corresponding to divergent mRNA/protein levels in these structures should be taken into account when tumor samples characterization estimatedby high-throughput methods.Electronic supplementary materialThe online version of this article (10.1186/s12895-018-0081-1) contains supplementary material, which is available to authorized users.

miRNAs in the Diagnosis and Prognosis of Skin Cancer

“…MiR-146a-5p regulates several important cellular pathways like Toll-like receptor, NF-κB, and ErB. Actually, miRNA-146a-5p targets almost 40 genes, one of them being the well-known NRAS gene (Aksenenko et al, 2019). Prognostic miRNA tissue signatures that match the recent ones were reported several years ago.…”

Genetic Characteristic and RNA-Seq Analysis in Transparent Mutant of Carp–Goldfish Nucleocytoplasmic Hybrid

“…In our present study, DEMs analysis found that miR-146a and miR-153b were both more highly detected in TM compared to those in WT. In mammals, recent studies have reported that miR-146a played an important role in melanoma [39,40,41] and retinal pigment epithelial cells [42]. Similarly, miR-153 could suppress cell proliferation and invasion by targeting snail family transcriptional repressor 1 (SNAI1) in melanoma [43].…”

Liquid Biopsy for Solid Ophthalmic Malignancies: An Updated Review and Perspectives

“…Mi-RNA-146a has been previously incriminated in other malignancies, such as papillary thyroid cancer, hepatocellular carcinoma, or leukemia [62]. Mi-RNA-146a has also been involved in the pigmentation and survival of UM cells [63]. However, other studies did not support mi-RNA-146a as being a useful blood biomarker [56,64].…”