SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A
SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A
复制标题
DOI：
10.3892/ol.2018.7989
复制
发表时间：
2018-04-01
期刊：
影响因子：
2.9
通讯作者：
Li, Jie
中科院分区：
文献类型：
--
作者：
Liu, Wenguang;Wu, Manwu;Li, Jie
沉默信息调节因子6(SIRT6)因其在抑制癌基因表达中的作用而被广泛认为是一种肿瘤抑制因子。然而，SIRT6在结直肠癌干细胞(CSCs)中的作用仍不明确。本研究证实SIRT6在大肠CSCs中的表达降低。SIRT6在大肠CSCs中的过表达不能诱导细胞凋亡。但SIRT6可显著抑制结直肠癌细胞的增殖和集落形成，并诱导G0/G1期停滞。此外，SIRT6还抑制了细胞分裂周期25A(CDC25A)的表达。染色质免疫沉淀实验表明，SIRT6直接与CDC25A启动子结合，降低了组蛋白H3赖氨酸9的乙酰化水平，提示SIRT6通过靶向CDC25A抑制结直肠癌干细胞的增殖。
Silent information regulator 6 (SIRT6) is broadly considered as a tumor suppressor due to its function in the suppression of oncogene expression. However, the role of SIRT6 in colorectal cancer stem cells (CSCs) remains uncharacterized. In the present study, it was demonstrated that SIRT6 expression was reduced in colorectal CSCs. Overexpression of SIRT6 in colorectal CSCs did not induce cell apoptosis. However, SIRT6 significantly inhibited cell proliferation, colony formation and induced G0/G1 phase arrest in colorectal CSCs. In addition, SIRT6 repressed the expression of cell division cycle 25A (CDC25A), an oncogenic phosphatase. Chromatin immunoprecipitation experiments indicated that SIRT6 directly bound to the CDC25A promoter and decreased the acetylation level of histone H3 lysine 9. Altogether, these data indicated that SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A.