Genetics and epigenetics of melanoma

Zhang, Xiaoying; Zhang, Pei-Ying

doi:10.3892/ol.2016.5093

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…EGFR, OPN and tenascin C have crucial role in the focal adhesion pathway, the multiprotein focal adhesion complexes silenced by OPN-siRNA can promote the connection between the extracellular matrix and cytoskeleton, and functionally control cell proliferation, differentiation, and motility [65]. Alterations of these pathways are significantly important in the pathogenesis of melanoma by affecting tumorigenesis, cellular growth, chemoresistance, invasion and migration [1,66].…”

Section: Discussionmentioning

confidence: 99%

“…This is followed by the survival of tumor cells in the circulatory system and their extravasation into distant tissues, where they may be able to proliferate [13 – 15] . OPN enhances the survival of cancer cells through its interaction with CD44 isoforms (CD44v) on the cell surface [16 , 17] , and it can promote tumor metastasis by interacting with different types of integrins (αvβ1, αvβ3, αvβ5, and α5β1) [18 , 19] . However, the molecular mechanism through which OPN promotes the invasion and metastasis formation of cutaneous melanoma remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Silencing Osteopontin Expression Inhibits Proliferation, Invasion and Induce Altered Protein Expression in Melanoma Cells

Kiss

Jámbor

Koroknai

et al. 2021

Pathol. Oncol. Res.

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Osteopontin (OPN) is a multifunctional phosphoprotein that is expressed in different types of cancers, including melanoma. OPN overexpression is associated with tumor progression and metastasis formation; however, the role of OPN in cell invasion and metastasis formation is not completely understood. In this study we aimed to define OPN expression in melanoma tissues and cell lines and investigate the effect of OPN expression on cell proliferation and invasion after inhibiting OPN expression with small interfering RNA (siRNA). OPN gene expression was determined by qRT-PCR, while protein expression was examined using a Proteome Profiler Oncology Array. siRNA-mediated OPN knockdown led to decreased OPN expression in melanoma cell lines, which was associated with decreased cell proliferation and invasion. Proteome profile analysis revealed significantly different protein expression between the original and transfected cell lines. The altered expression of the differently expressed proteins was validated at the mRNA level. Furthermore, OPN-specific siRNA was able to reduce OPN expression and inhibit the invasiveness of melanoma cells. Our results revealed for the first time that silencing the OPN gene influences proliferation and invasion of melanoma cells by effecting EGFR, tenascin C, survivin, galectin-3 and enolase 2 expression. To predict protein-protein interactions along with putative pathways we used STRING analysis for the differentially expressed proteins. These proteins formed multiple clusters, including extracellular matrix organization, regulation of angiogenesis, cell death and cell migration, PI3K-Akt, MAPK and focal adhesion signaling pathways. Taken together these data suggest that OPN might be an ideal target for drug development and therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Silencing Osteopontin Expression Inhibits Proliferation, Invasion and Induce Altered Protein Expression in Melanoma Cells

Kiss

Jámbor

Koroknai

et al. 2021

Pathol. Oncol. Res.

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“…Melanoma is a malignant skin tumor that arises from melanocytes (8). Though melanoma accounts for less than 5% of all cutaneous malignancies, it is the most lethal, representing 75% of all deaths due to skin cancer (1,9).…”

Section: Introductionmentioning

confidence: 99%

Exposure to Trace Elements and Risk of Skin Cancer: A Systematic Review of Epidemiologic Studies

Matthews

Fitch

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Exposure to environmental trace elements has been studied in relation to many cancers. However, an association between exposure to trace elements and skin cancer remains less understood. Therefore, we conducted a systematic review of published epidemiologic literature examining the association between exposure to trace elements, and risk of melanoma and keratinocyte carcinoma in humans. We identified epidemiologic studies investigating exposure to arsenic, cadmium, chromium, copper, iron, selenium, and zinc and risk of skin cancer in humans. Among the minerals, arsenic, selenium, and zinc had more than 5 studies available. Exposure to arsenic was associated with increased risk of keratinocyte carcinoma, while too few studies existed on melanoma to draw conclusions. Exposure to selenium was associated with possible increased risk of keratinocyte carcinoma. Studies of zinc and skin cancer were case-control in design and were found to have inconsistent associations. The data on the association between cadmium, chromium, copper, and iron and risk of skin cancer remain too sparse to draw any conclusions. In summary, epidemiologic studies on exposure to trace elements and cutaneous malignancies are limited. Studies with larger sample sizes and prospective designs are warranted to improve our knowledge of trace elements and skin cancer.

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“…Melanoma is a malignant tumor of melanocytes whose incidence is increasing worldwide, therefore attracting major interest in the current research [8]. With metastasis, both genetic and epigenetic alterations become relevant.…”

Section: Introductionmentioning

confidence: 99%

Network assessment of demethylation treatment in melanoma: Differential transcriptome-methylome and antigen profile signatures

et al. 2018

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BackgroundIn melanoma, like in other cancers, both genetic alterations and epigenetic underlie the metastatic process. These effects are usually measured by changes in both methylome and transcriptome profiles, whose cross-correlation remains uncertain. We aimed to assess at systems scale the significance of epigenetic treatment in melanoma cells with different metastatic potential.Methods and findingsTreatment by DAC demethylation with 5-Aza-2’-deoxycytidine of two melanoma cell lines endowed with different metastatic potential, SKMEL-2 and HS294T, was performed and high-throughput coupled RNA-Seq and RRBS-Seq experiments delivered differential profiles (DiP) of both transcriptomes and methylomes. Methylation levels measured at both TSS and gene body were studied to inspect correlated patterns with wide-spectrum transcript abundance levels quantified in both protein coding and non-coding RNA (ncRNA) regions. The DiP were then mapped onto standard bio-annotation sources (pathways, biological processes) and network configurations were obtained. The prioritized associations for target identification purposes were expected to elucidate the reprogramming dynamics induced by the epigenetic therapy. The interactomic connectivity maps of each cell line were formed to support the analysis of epigenetically re-activated genes. i.e. those supposedly silenced by melanoma. In particular, modular protein interaction networks (PIN) were used, evidencing a limited number of shared annotations, with an example being MAPK13 (cascade of cellular responses evoked by extracellular stimuli). This gene is also a target associated to the PANDAR ncRNA, therapeutically relevant because of its aberrant expression observed in various cancers. Overall, the non-metastatic SKMEL-2 map reveals post-treatment re-activation of a richer pathway landscape, involving cadherins and integrins as signatures of cell adhesion and proliferation. Relatively more lncRNAs were also annotated, indicating more complex regulation patterns in view of target identification. Finally, the antigen maps matched to DiP display other differential signatures with respect to the metastatic potential of the cell lines. In particular, as demethylated melanomas show connected targets that grow with the increased metastatic potential, also the potential target actionability seems to depend to some degree on the metastatic state. However, caution is required when assessing the direct influence of re-activated genes over the identified targets. In light of the stronger treatment effects observed in non-metastatic conditions, some limitations likely refer to in silico data integration tools and resources available for the analysis of tumor antigens.ConclusionDemethylation treatment strongly affects early melanoma progression by re-activating many genes. This evidence suggests that the efficacy of this type of therapeutic intervention is potentially high at the pre-metastatic stages. The biomarkers that can be assessed through antigens seem informative depending on the metastati...

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Genetics and epigenetics of melanoma

Cited by 9 publications

References 31 publications

Silencing Osteopontin Expression Inhibits Proliferation, Invasion and Induce Altered Protein Expression in Melanoma Cells

Silencing Osteopontin Expression Inhibits Proliferation, Invasion and Induce Altered Protein Expression in Melanoma Cells

Exposure to Trace Elements and Risk of Skin Cancer: A Systematic Review of Epidemiologic Studies

Network assessment of demethylation treatment in melanoma: Differential transcriptome-methylome and antigen profile signatures

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