SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A

Liu,Wenguang; Wu,Manwu; Du,Hechun; Shi,Xiaoliang; Zhang,Tao; Li,Jie

doi:10.3892/ol.2018.7989

SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A

Authors:
- Wenguang Liu
- Manwu Wu
- Hechun Du
- Xiaoliang Shi
- Tao Zhang
- Jie Li
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Affiliations: Department of General Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China, Genetics Department, Shaoxing Women and Children's Hospital, Shaoxing, Zhejiang 312000, P.R. China
Published online on: February 7, 2018 https://doi.org/10.3892/ol.2018.7989
Pages: 5368-5374

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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.

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