The Role of Circular RNAs in Keratinocyte Carcinomas

SIMPLE SUMMARY: Keratinocyte carcinomas include BCC and cSCC and represent the most frequent cancer among fair-skinned people. Tumor development is associated with mutations and dysregulation of many genes involved in biological processes such as cell proliferation, differentiation and apoptosis. The expression of these genes is controlled in many ways, including transcriptional and post-transcriptional control by circular RNAs. In recent studies, a number of circular RNAs have been identified that are dysregulated in BCC and cSCC. Biological functions relevant to tumor development were shown for some of these circRNAs, which may represent biomarkers for disease progression and targets for novel treatment approaches. ABSTRACT: Keratinocyte carcinomas (KC) include basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (cSCC) and represents the most common cancer in Europe and North America. Both entities are characterized by a very high mutational burden, mainly UV signature mutations. Predominately mutated genes in BCC belong to the sonic hedgehog pathway, whereas, in cSCC, TP53, CDKN2A, NOTCH1/2 and others are most frequently mutated. In addition, the dysregulation of factors associated with epithelial to mesenchymal transition (EMT) was shown in invasive cSCC. The expression of factors associated with tumorigenesis can be controlled in several ways and include non-coding RNA molecules, such as micro RNAs (miRNA) long noncoding RNAs (lncRNA) and circular RNAs (circRNA). To update findings on circRNA in KC, we reviewed 13 papers published since 2016, identified in a PubMed search. In both BCC and cSCC, numerous circRNAs were identified that were differently expressed compared to healthy skin. Some of them were shown to target miRNAs that are also dysregulated in KC. Moreover, some studies confirmed the biological functions of individual circRNAs involved in cancer development. Thus, circRNAs may be used as biomarkers of disease and disease progression and represent potential targets of new therapeutic approaches for KC.