1200 SIRT7 epigenetically regulates MITF to promote melanoma growth

Abstract

Sirtuins comprise a family of NAD+-dependent protein deacetylases, among which SIRT6 and SIRT7 are exclusively located in nucleus and have attracted considerable attention for their great pathogenic importance in cancer. Our previous study has reported that aberrant SIRT6 expression contributed to melanoma growth by regulating AKT signaling and autophagy. However, whether another nucleus-located sirtuin SIRT7 is involved in melanoma development remains unknown. Herein, we first found that SIRT7 was significantly up-regulated in both melanoma tissues and cell lines, compared with melanocytic nevus and normal human melanocytes respectively. Moreover, the knockdown of SIRT7 led to impaired proliferative ability and colonigenic capacity of melanoma cells. Subsequently, we found that SIRT7 positively regulated MITF expression at the transcriptional level and the tumorigenic effect of SIRT7 was dependent on MITF pathway. Further mechanistic study showed that SIRT7 directly bond to promoters of the MITF locus and deacetylated H3K18Ac. Altogether, our results demonstrate that SIRT7 promotes melanoma growth by epigenetically regulating MITF.