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J Invest Dermatol. 2017 Sep;137(9):1965-1974. doi: 10.1016/j.jid.2017.04.025. Epub 2017 May 11.

MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligo.

Author information

1
Sanford Burnham Prebys Medical Discovery Institute, 6400 Sanger Road, Orlando, Florida, USA.
2
Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, Bordeaux, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1035, Biothérapies de Maladies Génétiques, Inflammatoires et Cancers (BMGIC), Immuno-dermatology ATIP-AVENIR, University of Bordeaux, Bordeaux, France.
3
Sanford Burnham Prebys Medical Discovery Institute, 6400 Sanger Road, Orlando, Florida, USA; Medical and Biological Laboratories, Nagoya, Japan.
4
Advanced Materials Processing and Analysis Center, Nanoscience and Technology Center, Materials Science and Engineering, College of Medicine, University of Central Florida, Orlando, Florida, USA.
5
Department of Dermatology, Florida State University College of Medicine, Orlando Regional Campus, Orlando, Florida, USA.
6
Sanford Burnham Prebys Medical Discovery Institute, 6400 Sanger Road, Orlando, Florida, USA. Electronic address: rperera@sbpdiscovery.org.

Abstract

Vitiligo is a common chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical causes, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. In this study we characterized the human vitiligo cell line PIG3V and the normal human melanocyte line HEM-l by RNA sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched microRNA-211, a known metabolic switch in nonpigmented melanoma cells, was severely down-regulated in vitiligo cell line PIG3V and skin biopsy samples from vitiligo patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were reciprocally up-regulated. microRNA-211 binds to PGC1-α 3' untranslated region locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated microRNA-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of microRNA-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.

PMID:
28502800
DOI:
10.1016/j.jid.2017.04.025
[Indexed for MEDLINE]
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