SIRT6通过靶向细胞周期蛋白磷酸酶25A（CDC25A）抑制结直肠癌干细胞增殖。
SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A.
作者信息
Liu Wenguang, Wu Manwu, Du Hechun, Shi Xiaoliang, Zhang Tao, Li Jie
机构信息
Department of General Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Department of Emergency Surgery, Linyi People's Hospital, Shandong University, Linyi, Shandong 276034, P.R. China.
出版信息
Oncol Lett. 2018 Apr;15(4):5368-5374. doi: 10.3892/ol.2018.7989. Epub 2018 Feb 7.
Abstract
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.
摘要
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）中的作用仍未明确。在本研究中，结果表明结直肠癌干细胞中SIRT6表达降低。在结直肠癌干细胞中过表达SIRT6并未诱导细胞凋亡。然而，SIRT6显著抑制了结直肠癌干细胞的细胞增殖、集落形成并诱导G0/G1期阻滞。此外，SIRT6抑制了细胞分裂周期25A（CDC25A）的表达，CDC25A是一种致癌磷酸酶。染色质免疫沉淀实验表明，SIRT6直接与CDC25A启动子结合，并降低了组蛋白H3赖氨酸9的乙酰化水平。总之，这些数据表明SIRT6通过靶向CDC25A抑制结直肠癌干细胞增殖。
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