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

Please use this identifier to cite or link to this item:
https://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-202105144644
Open Access logo originally created by the Public Library of Science (PLoS)
Title: MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors
Authors: Melnik, Bodo
John, Swen Malte
Carrera-Bastos, Pedro
Schmitz, Gerd
ORCID of the author: https://orcid.org/0000-0002-4501-1809
https://orcid.org/0000-0002-1325-1007
https://orcid.org/0000-0001-5406-9458
https://orcid.org/0000-0002-4218-1300
Abstract: 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.
Citations: 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.
URL: https://repositorium.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-202105144644
Subject Keywords: environment; epigenetics; exosome; melanoma; metabolic syndrome; microRNA-21; prevention; obesity; radiation; therapy
Issue Date: 29-Jul-2020
License name: Attribution 4.0 International
License url: http://creativecommons.org/licenses/by/4.0/
Type of publication: Einzelbeitrag in einer wissenschaftlichen Zeitschrift [article]
Appears in Collections:FB08 - Hochschulschriften
Open-Access-Publikationsfonds

Files in This Item:
File Description SizeFormat 
cancers_Melnik_etal_2020.pdf2,4 MBAdobe PDF
cancers_Melnik_etal_2020.pdf
Thumbnail
View/Open


This item is licensed under a Creative Commons License Creative Commons