SMC4 knockdown inhibits malignant biological behaviors of endometrial cancer cells by regulation of FoxO1 activity

Yani Yan; Cong Liu; Jian Zhang; Weiwei Li; Xiurong Yin; Lixia Dong; Shulan Pang; Xuefeng Li

doi:10.1016/j.abb.2021.109026

SMC4 knockdown inhibits malignant biological behaviors of endometrial cancer cells by regulation of FoxO1 activity

Arch Biochem Biophys. 2021 Nov 15:712:109026. doi: 10.1016/j.abb.2021.109026. Epub 2021 Sep 16.

Authors

Yani Yan¹, Cong Liu², Jian Zhang³, Weiwei Li², Xiurong Yin², Lixia Dong², Shulan Pang⁴, Xuefeng Li⁵

Affiliations

¹ Department of Reproductive Medicine, Maternal and Child Care Center of Qinhuangdao, Qinhuangdao, 066000, China. Electronic address: yaniyan82@163.com.
² Department of Reproductive Medicine, Maternal and Child Care Center of Qinhuangdao, Qinhuangdao, 066000, China.
³ Clinical Department, Qinhuangdao Mental Health Center, Qinhuangdao, 066000, China.
⁴ School of Public Health, North China University of Science and Technology, Tangshan, 063210, China.
⁵ Department of Ultrasonics, Maternal and Child Care Center of Qinhuangdao, Qinhuangdao, 066000, China.

PMID: 34506757
DOI: 10.1016/j.abb.2021.109026

Abstract

Structural maintenance of chromosomes 4 (SMC4) has an important role in chromosome condensation and segregation, which is involved in regulating multiple tumor development. However, the role of SMC4 in endometrial cancer is uncertain. The expression and prognostic value of SMC4 were predicted by UALCAN, Gene Expression Omnibus (GEO), The Human Protein Atlas and Kaplan Meier plotter tools. SMC4-related genes were analyzed by LinkedOmics, Gene Ontology (GO) annotations, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Forkhead box protein O1 (FoxO1) activity was suppressed by AS1842856 (AS). SMC4, Ki67, B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein (Bax), FoxO1, phosphorylated FoxO1 (p-FoxO1), and p27 protein levels were detected by Western blotting. Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) analyses. Cell apoptosis was measured using TUNEL analysis. SMC4 abundance was increased in endometrial cancer, and predicted a worse overall survival. SMC4 knockdown repressed proliferative ability of endometrial cancer cells and promoted cell apoptosis. SMC4 knockdown promoted FoxO1 transactivation by decreasing its phosphorylated level. Addition of AS inhibited FoxO1 activity by increasing the phosphorylated level of FoxO1. The inhibition of FoxO1 activity reversed the effect of SMC4 silencing on cell proliferation and apoptosis. In conclusion, SMC4 silencing restrained cell proliferation and facilitated apoptosis in endometrial cancer via regulating FoxO1 activity.

Keywords: Apoptosis; Endometrial cancer; FoxO1; Proliferation; SMC4.

MeSH terms

Adenosine Triphosphatases / genetics
Adenosine Triphosphatases / metabolism*
Apoptosis / physiology
Carcinogenesis / metabolism
Cell Line, Tumor
Cell Proliferation / physiology
Chromosomal Proteins, Non-Histone / genetics
Chromosomal Proteins, Non-Histone / metabolism*
Endometrial Neoplasms / metabolism*
Female
Forkhead Box Protein O1 / metabolism*
Gene Expression Regulation, Neoplastic / physiology*
Gene Knockdown Techniques
Humans
Transcriptional Activation / physiology

Substances

Chromosomal Proteins, Non-Histone
FOXO1 protein, human
Forkhead Box Protein O1
Adenosine Triphosphatases
SMC4 protein, human