• circulating biomarkers
• melanoma
• microRNAs
• miR-193a

According to the latest estimates, cancer is becoming an increasing health risk on a global scale. Consequently, novel cancer treatment modalities are urgently needed, especially for the treatment of metastatic solid tumors that are refractory to standard therapies. In detail, cutaneous melanoma is an aggressive and chemotherapy-resistant type of cancer. Although the development of new targeted therapies and immunologic agents has completely changed the melanoma management, the most important tasks will be to improve diagnosis and overcome acquired resistance by new multi-targeted therapies. In this context, the ability of microRNAs (miRNAs) to regulate several signaling pathways in cancer could gain relevance for the development of new therapies. Indeed, several evidences identified dysregulated miRNAs in cutaneous melanoma and studied their potential use as biomarkers, therapeutic targets, and drugs themselves. In this thesis, we investigated the relevance of miRNAs as circulating diagnostic biomarkers in melanoma patients, the specific role of one selected miRNA on melanoma cell lines and a new approach to deliver miRNAs in an in vivo model.
In Experimental Section I, a high diagnostic potential was revealed by five miRNAs significantly deregulated in plasma of melanoma patients compared to healthy controls. Furthermore, we identified a signature of three different miRNAs (miR-149-3p, miR-150-5p, and miR-193a-3p) that can be proposed as a useful diagnostic biomarker panel with a very low false negative rate and a very high true positive rate.
In Experimental Section II, we described for the first time in cutaneous melanoma cell lines the tumor suppressor role of miR-193a family, detecting their ability to regulate several pathways involved in melanoma progression. Indeed, miR-193a over-expression decreased cell viability, proliferation, and migration.
In the Experimental Section III, we focused on in vivo miRNA delivery developing a viral platform able to efficiently deliver functional miRNAs in an in vivo melanoma model and able to regulate PD-L1 expression.