Identification and functional analysis of exosomal miR-16-5p, miR-6721-5p, and miR-486-5p associated with immune infiltration for potential vitiligo theranostics

Abstract

Vitiligo is an autoimmune disorder, which is characterized by the chronic loss of melanocytes and subsequent lack of melanin from the skin or hair or both. The resultant depigmentation state of the skin causing irregular white patches deteriorates the vitiligo patients’ quality of life by major stigmatizing psychological impact. Despite tremendous studies for the past several decades, there has been a dearth of precise theranostics for vitiligo, which necessitates to revisit the molecular changes in vitiligo. Following advent of omics research, the examination of circulating non-coding RNAs including miRNAs has been enormously utilized for potential vitiligo therapeutic targets, however the expression profile of miRNAs and their target genes have not been studied at exosomal level in correlation with the differentially expressed genes (DEG) at the tissue level in vitiligo patients.

Exosomes are tiny extracellular vesicles, with diameter approximately 30–200 nm, which is released from various cell types, and found in different biofluids including blood serum and plasma. Notably, the exosomes have been found to mimic the constituents of their parent cells, enabling it an excellent theranostics platform for diseased condition. Therefore, we investigated the plasma exosomal miRNA and identified the target genes associated with immune infiltration in vitiligo patients compared to healthy subjects. In this study, 65 DEGs have been analyzed by heatmap, among which 44 genes are up-regulated and 21 are down-regulated, which are associated with melanin- biosynthetic and metabolic process. CENPN and SLIRP were found to be substantially correlated with immune cells viz. CD8+ T cells, M1-macrophage. Among several target genes by the exosomal miRNAs, SLIRP has been found to be associated with miR-16-5p, whereas CENPN has been found to be associated with miR-6721-5p, and miR-486-5p. Conclusively, the exosomal miR-16-5p, miR-6721-5p, and miR-486-5p could be potential theranostics targets for vitiligo.