MicroRNA Expression Patterns Related to Merkel Cell Polyomavirus Infection in Human Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is an aggressive and lethal type of neuroendocrine skin cancer. Mutated Merkel cell polyomavirus (MCV) is commonly found in MCC, and leads to upregulation of the survivin oncogene. However, ∼20% of MCC tumors do not have detectable MCV, suggesting alternative etiologies for this tumor type. In this study, our aim was to evaluate microRNA (miRNA) expression profiles and their associations with MCV status and clinical outcomes in MCC. We showed that miRNA expression profiles were distinct between MCV-positive (MCV+) and MCV-negative (MCV-) MCCs and further validated that miR-203, miR-30a-3p, miR-769-5p, miR-34a, miR-30a-5p, and miR-375 were significantly different. We also identified a subset of miRNAs associated with tumor metastasis and MCC-specific survival. Functionally, overexpression of miR-203 was found to inhibit cell growth, induce cell cycle arrest, and regulate survivin expression in MCV- MCC cells, but not in MCV+ MCC cells. Our findings reveal a mechanism of survivin expression regulation in MCC cells, and provide insights into the role of miRNAs in MCC tumorigenesis.