Long non-coding RNAs (lncRNAs) are a largely uncharacterized group of non-coding RNAs with diverse regulatory roles in various biological processes.,Recent observations have elucidated the functional roles of lncRNAs in cutaneous biology, e.g. in proliferation and differentiation of epidermal keratinocytes and in cutaneous wound repair.,Furthermore, the role of lncRNAs in keratinocyte-derived skin cancers is emerging, especially in cutaneous squamous cell carcinoma (cSCC), which presents a significant burden to health care services worldwide and causes high mortality as metastatic disease.,Elucidation of the functions of keratinocyte-specific lncRNAs will improve understanding of the molecular pathogenesis of epidermal disorders and skin cancers and can be exploited in development of new diagnostic and therapeutic applications for keratinocyte carcinomas.,In this review, we summarize the current evidence of functionally important lncRNAs in cutaneous biology and in keratinocyte carcinomas.
Primary human squamous cell carcinoma (SCCa) are heterogeneous invasive tumors with proliferating outer layers and inner differentiating cell masses.,To determine if tumor initiating cells (TIC) are present in SCCa, we utilized newly developed reliable in vitro and in vivo xenograft assays that propagate human SCCa, and demonstrated that a small subset of SCCa cells (~1%) expressing Prominin-1 (CD133) in the outer layers of SCCa were highly enriched for TIC (~1/400) compared to unsorted SCCa cells (TIC ~1/106).,Xenografts of CD133+ SCCa recreated the original SCCa tumor histology and organizational hierarchy, while CD133- cells did not, and only CD133+ cells demonstrated the capacity for self-renewal in serial transplantation studies.,We present a model of human SCCa in which tumor projections expand with outer leading edges that contain CD133+ TIC.,Successful cancer treatment will likely require that the TIC identified in cancers be targeted therapeutically.,The demonstration that TIC are present in SCCa and are enriched in a CD133-expressing subpopulation to our knowledge has not previously been reported.