Ming Mei, Qiang Lei, Zhao Baozhong, He Yu-Ying
Section of Dermatology, Department of Medicine, University of Chicago, Chicago, IL, USA.
Exp Dermatol. 2014 Mar;23(3):207-9. doi: 10.1111/exd.12323.
SIRT2 is a member of the mammalian sirtuin family (SIRT1-7). As compared with other sirtuins, SIRT2 is found primarily in the cytoplasm. It regulates multiple physiological processes. However, the precise role of SIRT2 in skin cancer remains unclear. Here, we show that SIRT2 is downregulated in human skin cancer as compared with normal skin. SIRT2 deletion increases tumor growth in mice. SIRT2 knockdown upregulates the stem cell marker Keratin 19 (K19) in keratinocytes. In mice, SIRT2 deletion up-regulates K19 and K15 while it down-regulates the differentiation marker Loricrin in both normal skin and tumors. In skin tumors but not normal skin, SIRT2 deletion up-regulates the stem cell marker CD34 and increases the number of Ki67-positive cells. These findings indicate that SIRT2 is a tumor suppressor in the skin. Our findings add new insights into the role of SIRT2 in the molecular pathogenesis of skin cancer.
SIRT2是哺乳动物沉默调节蛋白家族（SIRT1 - 7）的成员之一。与其他沉默调节蛋白相比，SIRT2主要存在于细胞质中。它调节多种生理过程。然而，SIRT2在皮肤癌中的确切作用仍不清楚。在此，我们发现与正常皮肤相比，SIRT2在人类皮肤癌中表达下调。SIRT2缺失会增加小鼠肿瘤的生长。SIRT2基因敲低会上调角质形成细胞中的干细胞标志物角蛋白19（K19）。在小鼠中，SIRT2缺失在正常皮肤和肿瘤中均上调K19和K15，同时下调分化标志物兜甲蛋白。在皮肤肿瘤而非正常皮肤中，SIRT2缺失上调干细胞标志物CD34并增加Ki67阳性细胞的数量。这些发现表明SIRT2是皮肤中的一种肿瘤抑制因子。我们的发现为SIRT2在皮肤癌分子发病机制中的作用增添了新的见解。
