Cutaneous melanoma (CM) is a very aggressive disease, often characterized by unresponsiveness to conventional therapies and high mortality rates worldwide.,The identification of the activating BRAFV600  mutations in approximately 50% of CM patients has recently fueled the development of novel small‐molecule inhibitors that specifically target BRAFV600 ‐mutant CM.,In addition, a major progress in CM treatment has been made by monoclonal antibodies that regulate the immune checkpoint inhibitors.,However, although target‐based therapies and immunotherapeutic strategies have yielded promising results, CM treatment remains a major challenge.,In the last decade, accumulating evidence points to the aberrant expression of different types of noncoding RNAs (ncRNAs) in CM.,While studies on microRNAs have grown exponentially leading to significant insights on CM biology, the role of circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) in this tumor is less understood, and much remains to be discovered.,Here, we summarize and critically review the available evidence on the molecular functions of circRNAs and lncRNAs in BRAFV600 ‐mutant CM and CM immunogenicity, providing recent updates on their functional role in targeted therapy and immunotherapy resistance.,In addition, we also include an evaluation of several algorithms and databases for prediction and validation of circRNA and lncRNA functional interactions.,In the last decade, accumulating evidence points to the aberrant expression of different types of noncoding RNAs in cutaneous melanoma (CM).,Here, we summarize and critically review the available evidence on the molecular functions of circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) in BRAFV600 ‐mutant CM and CM immunogenicity, providing recent updates on their functional role in targeted therapy and immunotherapy resistance.,In addition, we also include an evaluation of several algorithms and databases for prediction and validation of circRNA and lncRNA functional interactions.
Melanoma progression is associated with increased invasion and, often, decreased levels of microphthalmia-associated transcription factor (MITF).,Accordingly, downregulation of MITF induces invasion in melanoma cells, however little is known about the underlying mechanisms.,Here, we report for the first time that depletion of MITF results in elevation of intracellular GTP levels and increased amounts of active (GTP-bound) RAC1, RHO-A and RHO-C.,Concomitantly, MITF-depleted cells display larger number of invadopodia and increased invasion.,We further demonstrate that the gene for guanosine monophosphate reductase (GMPR) is a direct MITF target, and that the partial repression of GMPR accounts mostly for the above phenotypes in MITF-depleted cells.,Reciprocally, transactivation of GMPR is required for MITF-dependent suppression of melanoma cell invasion, tumorigenicity, and lung colonization.,Moreover, loss of GMPR accompanies downregulation of MITF in vemurafenib-resistant BRAFV600E-melanoma cells and underlies the increased invasion in these cells.,Our data uncover novel mechanisms linking MITF-dependent inhibition of invasion to suppression of guanylate metabolism.