Dataset Information

Differences in microRNA expression between melanoma and healthy adjacent skin.

ABSTRACT:

Background

The 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.

Methods

Formalin-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.

Results

A 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-?B 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.

Conclusions

Elucidation 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.

SUBMITTER: Aksenenko M

PROVIDER: S-EPMC6321655 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Differences in microRNA expression between melanoma and healthy adjacent skin.

Aksenenko Mariya M Palkina Nadezhda N Komina Anna A Tashireva Liubov L Ruksha Tatiana T

BMC dermatology 20190105 1

<h4>Background</h4>The 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 ...[more]

PMID: 30611259

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Project description:BackgroundThis study represents the first attempt to perform a profiling analysis of the intergenerational differences in the microRNAs (miRNAs) of primary cutaneous melanocytic neoplasms in young adult and older age groups. The data emphasize the importance of these master regulators in the transcriptional machinery of melanocytic neoplasms and suggest that differential levels of expressions of these miRs may contribute to differences in phenotypic and pathologic presentation of melanocytic neoplasms at different ages.MethodsAn exploratory miRNA analysis of 666 miRs by low density microRNA arrays was conducted on formalin fixed and paraffin embedded tissues (FFPE) from 10 older adults and 10 young adults including conventional melanoma and melanocytic neoplasms of uncertain biological significance. Age-matched benign melanocytic nevi were used as controls.ResultsPrimary melanoma in patients greater than 60 years old was characterized by the increased expression of miRs regulating TLR-MyD88-NF-kappaB pathway (hsa-miR-199a), RAS/RAB22A pathway (hsa-miR-204); growth differentiation and migration (hsa-miR337), epithelial mesenchymal transition (EMT) (let-7b, hsa-miR-10b/10b*), invasion and metastasis (hsa-miR-10b/10b*), hsa-miR-30a/e*, hsa-miR-29c*; cellular matrix components (hsa-miR-29c*); invasion-cytokinesis (hsa-miR-99b*) compared to melanoma of younger patients. MiR-211 was dramatically downregulated compared to nevi controls, decreased with increasing age and was among the miRs linked to metastatic processes. Melanoma in young adult patients had increased expression of hsa-miR-449a and decreased expression of hsa-miR-146b, hsa-miR-214*. MiR-30a* in clinical stages I-II adult and pediatric melanoma could predict classification of melanoma tissue in the two extremes of age groups. Although the number of cases is small, positive lymph node status in the two age groups was characterized by the statistically significant expression of hsa-miR-30a* and hsa-miR-204 (F-test, p-value < 0.001).ConclusionsOur findings, although preliminary, support the notion that the differential biology of melanoma at the extremes of age is driven, in part, by deregulation of microRNA expression and by fine tuning of miRs that are already known to regulate cell cycle, inflammation, Epithelial-Mesenchymal Transition (EMT)/stroma and more specifically genes known to be altered in melanoma. Our analysis reveals that miR expression differences create unique patterns of frequently affected biological processes that clearly distinguish old age from young age melanomas. This is a novel characterization of the miRnomes of melanocytic neoplasms at two extremes of age and identifies potential diagnostic and clinico-pathologic biomarkers that may serve as novel miR-based targeted modalities in melanoma diagnosis and treatment.

Project description:Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ? 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular complications, or duration of DM, may further compromise tissue's healing ability leading to development of DFUs.

Dataset Information

Differences in microRNA expression between melanoma and healthy adjacent skin.

Background

Methods

Results

Conclusions

Publications

Differences in microRNA expression between melanoma and healthy adjacent skin.

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