miRNAs in the Diagnosis and Prognosis of Skin Cancer

Abstract

Skin cancer is, at present, the most common type of malignancy in the Caucasian population. Its incidence has increased rapidly in the last decade for both melanoma and non-melanoma skin cancer. Differential expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers, including skin cancers. Since miRNAs' discovery as regulators of gene expression, their importance grew in the field of oncology. miRNAs can post-transcriptionally regulate gene expression, tumor initiation, development progression, and aggressiveness. Nowadays, these short regulatory RNAs are perceived as one of the epigenetic markers for the identification of new diagnostic and/or prognostic molecular markers. Moreover, as miRNAs can drive tumorigenesis, they might eventually represent new therapy targets. Some miRNAs are pleiotropic, such as miR-214, which was found deregulated in several other tumors besides skin cancers. Some others are specific for one or more skin cancer types, like miR-21 and miR-221 for cutaneous melanoma and cutaneous squamous carcinoma or miR-155 for melanoma and cutaneous lymphoma. The goal of this review was to summarize some of the main miRNA detection technologies that are used to evaluate miRNAs in tissues and body fluids. Furthermore, their quantification limits, conformity, and robustness are discussed. Aberrant miRNA expression is analyzed for cutaneous melanoma, cutaneous squamous cell carcinoma (CSCC), skin lymphomas, cutaneous lymphoma, and Merkel cell carcinoma (MCC). In this type of disease, miRNAs are described as potential biomarkers to diagnose early lesion and/or early metastatic disease. In the future, whether in tissue or circulating in body fluids, miRNAs will gain their place in skin cancer diagnosis, prognosis, and future therapeutic targets.

Keywords: Merkel cell carcinoma; cutaneous lymphoma; cutaneous melanoma; cutaneous squamous carcinoma; miRNA.

FIGURE 1

Main technologies used in miRNA identification. Graphical representation of several miRNAs identified per sample versus a number of concomitantly analyzed samples. Technologies like RT-qPCR identify a few types of miRNAs, but in a large set of samples, miRNA multiplexing can identify hundreds of miRNAs in hundreds of different samples, while microarrays and sequencing can identify up to hundreds of thousands of miRNAs in hundreds of different samples.

FIGURE 2

Overview of the main miRNAs and the regulated genes that are identified in melanoma, in squamous cell carcinoma, and in cutaneous lymphoma. The first panel of oncomirs represents the miRNAs that regulate pro-tumoral genes in melanoma, squamous cell carcinoma, and in cutaneous lymphoma. The second panel represents tumor suppressor miRNAs regulating genes that are involved in anti-tumoral processes in squamous cell carcinoma and in cutaneous lymphoma.