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MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors

1
Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Am Finkenhügel 7a, D-49076 Osnabrück, Germany
2
Institute for Interdisciplinary Dermatological Prevention and Rehabilitation (iDerm) at the University of Osnabrück, Am Finkenhügel 7a, D-49076 Osnabrück, Germany
3
Lower-Saxonian Institute of Occupational Dermatology (NIB), Am Finkenhügel 7a, D-49076 Osnabrück, Germany
4
Department of Clinical Sciences, Lund University, Jan Waldenströms gata 35, CRC, hus 28 plan 11, 205 02 Malmö, Sweden
5
Institute for Clinical Chemistry and Laboratory Medicine, University Hospital, Regensburg, University of Regensburg, Franz-Josef-Strauß-Allee 11, D-93053 Regensburg, Germany
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(8), 2111; https://doi.org/10.3390/cancers12082111
Received: 28 June 2020 / Revised: 16 July 2020 / Accepted: 24 July 2020 / Published: 29 July 2020
(This article belongs to the Section Molecular Cancer Biology)
DNA mutation-induced activation of RAS-BRAF-MEK-ERK signaling associated with intermittent or chronic ultraviolet (UV) irradiation cannot exclusively explain the excessive increase of malignant melanoma (MM) incidence since the 1950s. Malignant conversion of a melanocyte to an MM cell and metastatic MM is associated with a steady increase in microRNA-21 (miR-21). At the epigenetic level, miR-21 inhibits key tumor suppressors of the RAS-BRAF signaling pathway enhancing proliferation and MM progression. Increased MM cell levels of miR-21 either result from endogenous upregulation of melanocytic miR-21 expression or by uptake of miR-21-enriched exogenous exosomes. Based on epidemiological data and translational evidence, this review provides deeper insights into environmentally and metabolically induced exosomal miR-21 trafficking beyond UV-irradiation in melanomagenesis and MM progression. Sources of miR-21-enriched exosomes include UV-irradiated keratinocytes, adipocyte-derived exosomes in obesity, airway epithelium-derived exosomes generated by smoking and pollution, diet-related exosomes and inflammation-induced exosomes, which may synergistically increase the exosomal miR-21 burden of the melanocyte, the transformed MM cell and its tumor environment. Several therapeutic agents that suppress MM cell growth and proliferation attenuate miR-21 expression. These include miR-21 antagonists, metformin, kinase inhibitors, beta-blockers, vitamin D, and plant-derived bioactive compounds, which may represent new options for the prevention and treatment of MM. View Full-Text
Keywords: environment; epigenetics; exosome; melanoma; metabolic syndrome; microRNA-21; prevention; obesity; radiation; therapy environment; epigenetics; exosome; melanoma; metabolic syndrome; microRNA-21; prevention; obesity; radiation; therapy
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MDPI and ACS Style

Melnik, B.C.; John, S.M.; Carrera-Bastos, P.; Schmitz, G. MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors. Cancers 2020, 12, 2111. https://doi.org/10.3390/cancers12082111

AMA Style

Melnik BC, John SM, Carrera-Bastos P, Schmitz G. MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors. Cancers. 2020; 12(8):2111. https://doi.org/10.3390/cancers12082111

Chicago/Turabian Style

Melnik, Bodo C.; John, Swen M.; Carrera-Bastos, Pedro; Schmitz, Gerd. 2020. "MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors" Cancers 12, no. 8: 2111. https://doi.org/10.3390/cancers12082111

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