Signaling Pathways Altered During the Metastatic Progression of Melanoma

that appears to act as a metastamiR in melanoma is the miR-214. MiR-214 expression was evaluated in the poorly metastatic lineage A375 and in its highly metastat‐ ic variant cell lines, originated from several passages in vivo . It was seen an upregulation of miR-214 in the highly metastatic melanoma cells lines in comparison with the parental one. Beyond that, the overexpression of miR-214 in a metastatic lineage that expressed intermediate levels of this miRNA resulted in a higher number of lung metastases than the control in a metastasis formation assay in vivo . In addition, miR-214 silencing in a highly metastatic lineage, which expressed high levels of this miRNA, caused a significantly reduction of lung metastases formation. Furthermore, as primary tumor growth was not influenced by miR-214, these results indicate miR-214 as a metastamiR with an important role in the melanoma progression [119].