| Summary: | <i>MicroRNA-375</i> (<i>miR-375</i>) is deregulated in multiple tumor types and regulates important targets involved in tumorigenesis and metastasis. This miRNA is highly expressed in Merkel cell carcinoma (MCC) compared to normal skin and other non-MCC skin cancers, and its expression is high in Merkel cell polyomavirus (MCPyV)-positive (MCPyV+) and low in MCPyV-negative (MCPyV−) MCC tumors. In this study, we characterized the function and target of <i>miR-375</i> in MCPyV+ and MCPyV− MCC cell lines. Ectopic expression of <i>miR-375</i> in MCPyV− MCC cells resulted in decreased cell proliferation and migration, as well as increased cell apoptosis and cell cycle arrest. However, in MCPyV+ MCC cells, inhibition of <i>miR-375</i> expression reduced cell growth and induced apoptosis. Additionally, the expression of lactate dehydrogenase B (<i>LDHB</i>), a known target of <i>miR-375</i>, was inversely correlated with <i>miR-375</i>. Silencing of LDHB reduced cell growth in MCPyV− cell lines, while its silencing in MCPyV+ cell lines rescued the cell growth effect mediated by <i>miR-375</i> inhibition. Together, our results suggest dual roles of <i>miR-375</i> and LDHB in MCPyV and non-MCPyV-associated MCCs. We propose that LDHB could be a therapeutic target in MCC and different strategies should be applied in virus- and non-virus-associated MCCs.
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