MIR-193A MIMICS AS NEW POTENTIAL THERAPEUTIC AGENTS IN CUTANEOUS MELANOMA

MicroRNAs (miRNAs) are a class of small, non-coding RNAs that nega- tively regulate gene and other non-coding transcripts expression. MiR- NAs play relevant functions in cancer biology and “miRNA mimics” may represent new potential innovative therapeutic agents restoring nor- mal function of endogenous tumor suppressive miRNAs1 MiR-193a acts as tumour suppressor in different types of cancer.2–4 In melanoma, it is down-expressed in tissues and in plasma of patients,5,6 but its role as oncosuppressor has not been yet clearly established. Aim of this study was to analyse the effects of miR-193a mimics transfection in melanoma cells to evaluate their potential role as therapeutic agents against cuta- neous melanoma. miR-193a-3p and miR-193a-5p mimics were trans- fected with lipofectamine in three different melanoma cell lines with different B-RAF mutation status. Their effects on cell viability and migration, p-Akt, p-Erk, B-Raf protein levels and epithelial-mesenchy- mal transition (EMT) were evaluated. A significant decrease of cell via- bility and migration ability was induced by both miR-193a mimics in transfected cells. In addition, they decreased B-Raf protein levels and phosphorylation of Akt and Erk proteins. Finally, also Vimentin and E- Cadherin protein levels were significantly changed in transfected-cells: Vimentin expression was significantly reduced, while E-cadherin expres- sion was significantly increased. Overall our results indicate the potential of both miRNA mimics to interfere with melanoma cell proliferation, survival and metastatization, independently from B-RAF mutation status of melanoma cells. So, our data suggest that miR193a mimics may repre- sent potential therapeutic agents reducing melanoma progression. Future experiments will be aimed at investigating this therapeutic strategy in an in vivo cutaneous melanoma model. References: [1] Maitri et al., (2016) EBioMedicine; 12: 34–42. [2] Williams et al., (2015) Oncotarget; 6(27):23480–95. [3] Jian et al., (2016) Tumour Biol.; Jul;37(7):8941–9. [4] Yu et al., (2015) Oncogene; 34(4):413–23. [5] Caramuta et al. (2010) J Invest Dermatol.;130(8):2062–70. [6] Fogli et al., (2017) Tumour Biol.;39(5):1010428317701646.