Abstract

Objectives: Our research explores the epigenetic regulation of skin pigmentation in Chinese individuals under UV exposure. We profiled miRNA expression and identified one miRNA signature linked to pigmentation and investigated the potential of 4-Butylresorcinol (577) to modulate its expression. By targeting this pathway, we aim to influence key melanogenesis genes—TYR, TYRP1, and MITF—offering a novel upstream approach to inhibit melanin synthesis. This study addresses pigmentation concerns relevant to biological aging, as well as cosmetic and aesthetic procedures in the Asian population. Introduction: East Asian populations often show more hyperpigmented spots during photoaging compared to Europeans, and post-inflammatory hyperpigmentation is frequent after aesthetic procedures. Melanogenesis involves a complex network of genes, including TYR, TYRP1, and MITF, whom expressions are regulated by the environment. Current whitening agents mainly act by directly inhibiting tyrosinase, yet no approach has demonstrated an upstream epigenetic mechanism. Our research aims to fill this knowledge gap by exploring novel regulatory pathways in pigmentation control. Materials / method: We collected photo-exposed and photo-protected skin biopsies from 15 Chinese women (30–40 years) in Shanghai undergoing blepharoplasty and abdominoplasty. Using microarray profiling, we identified UV-related miRNA signatures and, through in silico predictions, linked them to key melanogenesis genes. These predictions were validated in vitro on human melanocytes. On the same model, we tested 4-Butylresorcinol (577), confirming its efficacy on miRNA expression and the regulation of TYR, TYRP1, and MITF gene expression. Results: UV radiation alters miRNA expression and impacts melanogenesis. Our study identified hsa‑miR‑16-2-3p as a pigmentation-related signature in Chinese individuals under UV exposure. In vitro tests on melanocytes showed that elevated hsa‑miR‑16-2-3p expression correlates with increased TYR, TYRP1, and MITF gene activity. Further experiments demonstrated that 4-Butylresorcinol (577) reduced hsa‑miR‑16-2-3p expression by 40% (p<0.05), thereby regulating key melanogenesis genes and supporting its potential for a skin-whitening effect. Conclusion: Our findings indicate that microRNA miR-16-2-3p may act as a biomarker of skin pigmentation in Chinese females under UV exposure. We identified an epigenetic mechanism of action for 4-Butylresorcinol (577), showing its potential to regulate pigmentation through miRNA modulation. This case study paves the way for a new generation of epigenetic-based skincare capable of inhibiting melanin synthesis upstream, addressing pigmentation changes linked to biological aging in Asian populations and supporting dermatological procedures prone to hyperpigmentation.