Serum levels of miRNA-21-5p in vitiligo patients and effects of miRNA-21-5p on SOX5, beta-catenin, CDK2 and MITF protein expression in normal human melanocytes.

Abstract

BACKGROUND:

Epigenetics of vitiligo was evaluated in few studies. In particular, the role of miR-21, a microRNA involved in various processes, including melanogenesis, was never investigated.

OBJECTIVE:

Evaluation of serum levels of miR-21-5p in vitiligo patients and miR-21-5p effects on melanogenesis.

METHODS:

We measured serum levels of miR-21-5p in 40 patients affected by nonsegmental vitiligo and 40 sex- and age-matched healthy controls. Next, normal human melanocytes were transfected with miR-21-5p to study the effects of this microRNA, which targeted some proteins involved in melanogenesis pathway like SOX5, beta-catenin, cyclin-dependent kinase 2 (CDK2), and MITF.

RESULTS:

The expression of miR-21-5p in vitiligo patients was 3.6-4454.4 fold (mean 990.4 ± 1397.9) higher than in controls. The relative expression of miR-21-5p was directly and significantly correlated with disease severity, defined by VASI (Vitiligo Area and Severity Index) score (Rho = 0.89, p = 10-7), but not other individual or clinical characteristics. In the second part of the study, a significant reduction of SOX5, beta-catenin and CDK2 protein expression and increase of MITF protein expression was observed in cultured melanocytes after 24 h trasfection with miR-21-5p.

CONCLUSION:

According to literature, miR-21-5p upregulation and consequent SOX5 downregulation should upregulate melanogenesis, while vitiligo is characterized by skin depigmentation. Our results suggest that current knowledge of the pathogenesis of vitiligo is probably incomplete. Clinical manifestations could result from an altered balance between metabolic pathways with contrasting effects. In this view, miR-21-5p upregulation might be a tentative compensation mechanism. Further studies appear necessary to confirm and better understand our results and their importance.

• Authors: M'Hammed Aguennouz, Fabrizio Guarneri, Rosaria Oteri, Francesca Polito, Roberta Giuffrida, Serafinella P Cannavò
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 101 Issue 1 Pg. 22-29 (Jan 2021) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 33176966 (Publication Type: Journal Article, Observational Study)
• Copyright: Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Chemical References

• CTNNB1 protein, human
• Cell-Free Nucleic Acids
• MIRN21 microRNA, human
• MITF protein, human
• Melanins
• MicroRNAs
• Microphthalmia-Associated Transcription Factor
• SOX5 protein, human
• SOXD Transcription Factors
• beta Catenin
• CDK2 protein, human
• Cyclin-Dependent Kinase 2

Topics

• Adolescent
• Adult
• Case-Control Studies
• Cell Line
• Cell-Free Nucleic Acids (blood, metabolism)
• Cyclin-Dependent Kinase 2 (genetics)
• Gene Expression Regulation
• Humans
• Melanins (biosynthesis)
• Melanocytes (metabolism)
• MicroRNAs (blood, metabolism)
• Microphthalmia-Associated Transcription Factor (genetics)
• Pilot Projects
• SOXD Transcription Factors (genetics)
• Severity of Illness Index
• Skin (cytology, pathology)
• Skin Pigmentation (genetics)
• Vitiligo (blood, diagnosis, genetics, pathology)
• Young Adult
• beta Catenin (genetics)