Molecular Mechanisms and Therapeutic Implications of Long Non-coding RNAs in Cutaneous Biology and Disease

Abstract

Human skin is the largest organ of the human body and accounts for approximately fifteen percent of the total bodyweight. Its main physiological role is to protect the body against a wide range of environmental factors including pathogens, ultraviolet light, and injury. Importantly, the skin can regenerate and heal upon injury in large part by the differentiation of keratinocytes. Not surprisingly, dysregulation of cutaneous differentiation and self-renewal can result in a variety of skin-related pathologies, including autoimmune disease and cancer. Increasing evidence supports the premise that long non-coding RNAs (lncRNAs) act as critical mediators of gene expression and regulate important biological processes within the skin. Notably, dysregulation of lncRNAs has been shown to influence diverse physiological and pathological consequences. More recently, numerous reports have revealed new mechanistic insight on the role that lncRNAs play in skin homeostasis as well as their contribution to the pathogenesis of skin-related disorders. Here, we review the biological functions of cutaneous lncRNAs and their impact on skin homeostasis. We also describe the fundamental roles of lncRNAs in the pathogenesis of skin-related disorders, including fibrotic, autoimmune, and malignant diseases. Lastly, we will highlight how a better understanding of lncRNAs at the molecular level may reveal novel therapeutic approaches for the improvement of cutaneous disorders.

Keywords: cancer; cutaneous biology; differentiation; lncRNA; pathology; skin.

FIGURE 1 |. The impact of lncRNAs in the pathogenesis of hypertrophic scars (HSs).

A graphical illustration of the contribution of lncRNAs on the initiation and progression of HSs. Green arrows indicate an upregulation of lncRNAs, while red arrows indicate a downregulation of lncRNAs.

FIGURE 2 |. The role of lncRNAs in the pathogenesis of psoriasis.

A schematic diagram highlighting the mechanisms by which lncRNAs contribute to psoriasis. Green arrows indicate an upregulation of lncRNAs, while red arrows indicate a downregulation of lncRNAs.