794 Genetic expression profiling in the diagnosis of amelanotic melanoma: An emerging technology and a caution to potential increased reliance

Abstract

SIRT7 is a crucial nuclear-located histone deacetylase with great implications in regulating genome stability, RNA metabolism and mitochondrial function, and its dysregulated expression and function are associated with the pathogenesis of multiple cancers. However, the role of SIRT7 in melanoma progression and the underlying mechanism are far from understood. In the present study, we first found that SIRT7 expression was prominently increased in both melanoma cell lines and tissues compared with controls. Moreover, the knockdown of SIRT7 significantly suppressed melanoma cell proliferation and colony formation, as well as potentiated oxidative stress or ER stress-induced cell apoptosis. Forwardly, we showed that SIRT7 positively regulated the expression of MITF, and MITF deficiency reversed the facilitative role of SIRT7 in promoting melanoma cell proliferation. The influence of SIRT7 on MITF expression was associated with its impact on TGF-b-SMAD4 pathway and subsequent mediation of PAX3 transcriptional function. Overall, our data demonstrated that up-regulated SIRT7 expression contributed to melanoma growth by promoting MITF expression, and targeting SIRT7 could be potent therapeutic approach for melanoma therapy.