MicroRNA-driven deregulation of cytokine expression helps development of drug resistance in metastatic melanoma.

microRNAs are major components of the eukaryotic post-transcriptional machinery and are frequently deregulated during cancer development. Increasing evidence points to them also as key players in the establishment of drug resistance. In this review, we provide an updated overview of the role of miRNAs in melanoma development and drug resistance and postulate that they are able to drive these processes in concert with deregulation of inflammatory and angiogenic cytokine expression. Notably, we have identified by querying the Cancer Genome Atlas database, a defined set of miRNAs which mostly have an impact on the development of melanoma and have recognized the main downstream pathways controlled by them. Most importantly, these miRNAs, which are down-regulated in metastatic melanomas as compared to primary tumors, are also able to predict prognosis of BRAF-mutated melanoma patients. Finally, we discuss the possibility that a common miRNA signature characterizes not only acquired resistance to MAPKi but also innate resistance to anti-PD-1 immunotherapy, since these conditions are both associated with alterations of the same pro-angiogenetic and pro-inflammatory pathways.