Abstract B59: Role of Dicer on human melanoma progression and resistance

Abstract

Melanoma is a serious public health problem that affects the population of Latin America and is increasing rapidly compared to other types of tumors. The growth or change in this type of tumor is progressive and is in the horizontal and/or vertical direction. Breslow thickness (vertical staging) is the tumor thickness in the dermis where patients with lesion thickness less than 0.75 mm have good prognosis, unlike lesion thickness larger than 3 mm. This stage is classified into T (primary tumor): T0 (with no evidence of primary tumor); Tis (in situ melanoma); T1 (1 mm); T2 (1.01 to 2 mm); T3 (2.01 to 4 mm); and T4 (above 4 mm). Knowing some molecular markers of melanoma is essential for the identification of genetically predisposed individuals, as well as early detection of the disease. Recent works has demonstrated that microRNAs may be involved in modulation of melanoma. Dicer is an essential member of the RNase III family which controls maturation of miRNAs in the cytoplasm from microRNA precursors (pre-miRNAs). The upregulation of Dicer is associated with aggressive features and proliferation of melanoma and no other skin tumors such as carcinomas and sarcoma. In our present study, we found that the knockdown expression of Dicer using the CRISPR/CAS9 in melanoma cell line induced more chemosensitivity to cisplatin and these changes correlated with the downregulation of Dicer. We examined the consequence of Dicer knockdown on melanoma cell proliferation, clonogenic assays, and overall survival. We also compared Dicer in tissue from patients diagnosed with melanoma in different stages with the prognosis of these patients, suggesting that the reduction in Dicer expression is associated with melanoma progression. Considering the fundamental and multiple biologic roles of Dicer in various cellular processes, our results suggest that modulation of Dicer in melanoma should become a promising therapeutic candidate for further clinical application. Note: This abstract was not presented at the conference. Citation Format: Nathalia Cruz de Victo, Sandy Adjemian, Romulo dos Santos Sobreira Nunes, Rildo Aparecido Volpini, Mara Huffenbaecher Giavina-Bianchi, Cyro Festa Neto, Niels Olsen Saraiva Câmara, Gustavo Pessini Amarante-Mendes, Jacqueline de Fátima Jacysyn. Role of Dicer on human melanoma progression and resistance [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B59.