Melanomagenesis: multifaceted attacks on the genome

Bordelon, Jenna R.; Sánchez, Margarita Dorantes; Grichnik, James M.

doi:10.1111/exd.12600

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…Taken together, melanoma is a model cancer system not only involving genetic but also environmental components [ 258 ]. At the molecular level, miR-21 links environmental exposure to melanomagenesis.…”

Section: Discussionmentioning

confidence: 99%

MiR-21: an environmental driver of malignant melanoma?

Melnik

2015

J Transl Med

104

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Since the mid-1950’s, melanoma incidence has been rising steadily in industrialized Caucasian populations, thereby pointing to the pivotal involvement of environmental factors in melanomagenesis. Recent evidence underlines the crucial role of microRNA (miR) signaling in cancer initiation and progression. Increased miR-21 expression has been observed during the transition from a benign melanocytic lesion to malignant melanoma, exhibiting highest expression of miR-21. Notably, common BRAF and NRAS mutations in cutaneous melanoma are associated with increased miR-21 expression. MiR-21 is an oncomiR that affects critical target genes of malignant melanoma, resulting in sustained proliferation (PTEN, PI3K, Sprouty, PDCD4, FOXO1, TIPE2, p53, cyclin D1), evasion from apoptosis (FOXO1, FBXO11, APAF1, TIMP3, TIPE2), genetic instability (MSH2, FBXO11, hTERT), increased oxidative stress (FOXO1), angiogenesis (PTEN, HIF1α, TIMP3), invasion and metastasis (APAF1, PTEN, PDCD4, TIMP3). The purpose of this review is to provide translational evidence for major environmental and individual factors that increase the risk of melanoma, such as UV irradiation, chemical noxes, air pollution, smoking, chronic inflammation, Western nutrition, obesity, sedentary lifestyle and higher age, which are associated with increased miR-21 signaling. Exosomal miR-21 induced by extrinsic and intrinsic stimuli may be superimposed on mutation-induced miR-21 pathways of melanoma cells. Thus, oncogenic miR-21 signaling may be the converging point of intrinsic and extrinsic stimuli driving melanomagenesis. Future strategies of melanoma treatment and prevention should thus aim at reducing the burden of miR-21 signal transduction.

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Section: Discussionmentioning

confidence: 99%

MiR-21: an environmental driver of malignant melanoma?

Melnik

2015

J Transl Med

104

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“…However, it is also interesting that BRAF is not a UV signature mutation. The extent of UV mutations varies depending on neoplasm type, suggesting distinct mutagenic environments may drive the different melanoma subtypes [16,17].…”

Section: Data Supporting Skin Originmentioning

confidence: 99%

Conceptual Approach to Early Melanoma Detection: Models, Tools, Issues and Challenges

Damanpour

Grichnik

2015

Melanoma Manag.

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Identification and removal of melanoma early in its development remains the most effective treatment. However, identification of early melanoma remains challenging and may result in unnecessary morbidity due to the excess excision of benign melanocytic nevi. Herein, we present a conceptual model of benign and malignant melanocytic growths. The potential differences in the location of the cell of origin as well as considerations for neoplasm progression are also reviewed. Several of the clinical tools currently available, the integration of information from those different sources, and approaches to set an optimum biopsy threshold are discussed. While early detection remains a challenge, significant progress has been made. Insight into melanoma growth processes and appropriate use of available tools can result in the detection of thinner melanomas while also decreasing overall biopsy rates.

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