MicroRNA Cancer Regulation

Kunz M, Manfred Kunz M.D., Manfred Kunz

Ulf Schmitz, Olaf Wolkenhauer, Julio Vera

Malignant melanoma is a highly aggressive tumour with increasing -incidence and poor prognosis in the metastatic stage. In recent years, a substantial number of reports on individual miRNAs or miRNA patterns have been published providing strong evidence that miRNAs might play an important role in malignant melanoma and might help to better understand the molecular mechanisms of melanoma development and progression. A major preliminary finding was that melanoma-associated miRNAs are often located in genomic regions with frequent gains and losses in tumours. Detailed studies of different groups thereafter identified miRNAs with differential expression in benign melanocytes compared with melanoma cell lines or in benign melanocytic lesions compared with melanomas. Among these were let-7a and b, miR-23a and b, miR-148, miR-155, miR-182, miR-200c, miR-211, miR214, and miR-221 and 222. Some of these miRNAs target well-known melanoma-associated genes like the NRAS oncogene, microphthalmia-associated transcription factor (MITF), receptor tyrosine kinase c-KIT or AP-2 transcription factors (TFAP2). Although we are still far from a complete understanding of the role of miRNA-target gene interactions in malignant melanoma, these findings further underscore the notion of a direct involvement of miRNAs in melanoma biology. Very recently, a prognostic signature of six miRNAs has been identified consisting of miRNAs miR-150, miR-342-3p, miR-455-3p, miR-145, miR-155, and miR-497. High expression of these miRNAs was shown to be associated with improved long-term survival of metastatic patients.