MicroRNA-21-enriched exosomes as epigenetic regulators in melanomagenesis and melanoma progression : The impact of western lifestyle factors
(2020) In Cancers 12(8). p.1-40- 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... (More)
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.
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- author
- Melnik, Bodo C. ; John, Swen Malte ; Carrera-Bastos, Pedro LU and Schmitz, Gerd
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Environment, Epigenetics, Exosome, Melanoma, Metabolic syndrome, MicroRNA-21, Obesity, Prevention, Radiation, Therapy
- in
- Cancers
- volume
- 12
- issue
- 8
- article number
- 2111
- pages
- 40 pages
- publisher
- MDPI AG
- external identifiers
-
- pmid:32751207
- scopus:85090024231
- ISSN
- 2072-6694
- DOI
- 10.3390/cancers12082111
- language
- English
- LU publication?
- yes
- id
- f067c174-8bd3-4930-b1ca-46305a372d7a
- date added to LUP
- 2020-09-25 15:40:46
- date last changed
- 2024-04-03 13:27:16
@article{f067c174-8bd3-4930-b1ca-46305a372d7a,
abstract = {{<p>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.</p>}},
author = {{Melnik, Bodo C. and John, Swen Malte and Carrera-Bastos, Pedro and Schmitz, Gerd}},
issn = {{2072-6694}},
keywords = {{Environment; Epigenetics; Exosome; Melanoma; Metabolic syndrome; MicroRNA-21; Obesity; Prevention; Radiation; Therapy}},
language = {{eng}},
number = {{8}},
pages = {{1--40}},
publisher = {{MDPI AG}},
series = {{Cancers}},
title = {{MicroRNA-21-enriched exosomes as epigenetic regulators in melanomagenesis and melanoma progression : The impact of western lifestyle factors}},
url = {{http://dx.doi.org/10.3390/cancers12082111}},
doi = {{10.3390/cancers12082111}},
volume = {{12}},
year = {{2020}},
}