Skin-Derived Non-Coding RNAs as Potential Biomarkers and Therapeutic Targets

Skin-derived extracellular nucleic acids—particularly non-coding RNAs (ncRNAs) such as miRNAs and lncRNAs—are a rapidly evolving frontier in molecular diagnostics. These molecules are present in skin tissue, dermal interstitial fluid, and sweat, whilst ncRNAs regulate essential processes including epidermal differentiation, wound healing, immune regulation, and tumourigenesis, positioning them as promising candidates for minimally invasive biomarker development across a broad spectrum of dermatological diseases. This narrative review summarises their biological functions and potential clinical applications. The available evidence provides a conceptual basis for an emerging cutaneous “surface liquid biopsy” framework, whilst highlighting the need for standardised sampling, analytical validation, and clinical evaluation before such approaches can be translated into clinical practice. Although ample disease-associated ncRNA signatures have been uncovered, many remain at exploratory or early translational stages, and the concordance of these ncRNA signatures with corresponding blood and tissue biomarkers needs to be established. Continued advances in sampling strategies, analytical technologies, and clinical validation are needed to translate these findings into clinically deployable platforms for dermatological diseases and, potentially, systemic diseases in the future.