Open AccessSirtuin 2 in Endometrial Cancer: A Potential Regulator for Cell Proliferation, Apoptosis and RAS/ERK Pathway
Author(s) -
Yue Guo,
Nannan Zhao,
Jiayi Zhou,
Jie Dong,
Xing Wang
Publication year - 2020
Publication title -
technology in cancer research and treatment
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 63
eISSN - 1533-0346
pISSN - 1533-0338
DOI - 10.1177/1533033820980781
Subject(s) - sirt2 , mapk/erk pathway , cell growth , hras , apoptosis , transfection , cancer research , microbiology and biotechnology , biology , cell culture , sirtuin , signal transduction , western blot , chemistry , mutation , gene , acetylation , genetics , kras
Objective: The present study aimed to explore the function of sirtuin 2 (SIRT2) on cell proliferation, apoptosis, rat sarcoma virus (RAS)/ extracellular signal-regulated kinase (ERK) pathway in endometrial cancer (EC).Methods: SIRT2 expression in human EC cell lines and human endometrial (uterine) epithelial cell (HEEC) line was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. SIRT2 knock-down and control knock-down plasmids were transfected into HEC1A cells, respectively; SIRT2 overexpression and control overexpression plasmids were transfected into Ishikawa cells, respectively. After transfection, SIRT2, HRas proto-oncogene, GTPase (HRAS) expressions were evaluated by RT-qPCR and western blot. ERK and phosphorylated ERK (pERK) expressions were evaluated by western blot. Meanwhile, cell proliferation and cell apoptosis were measured.Results: Compared to normal HEEC cell line, SIRT2 mRNA and protein expressions were increased in most human EC cell lines (including HEC1A, RL952 and AN3CA), while were similar in Ishikawa cell line. In HEC1A cells, SIRT2 knock-down decreased cell proliferation but increased apoptosis. In Ishikawa cells, SIRT2 overexpression induced cell proliferation but inhibited apoptosis. For RAS/ERK pathway, SIRT2 knock-down reduced HRAS and inactivated pERK in HEC1A cells, whereas SIRT2 overexpression increased HRAS and activated pERK in Ishikawa cells, suggesting that SIRT2 was implicated in the regulation of RAS/ERK pathway in EC cells.Conclusion: SIRT2 contributes to the EC tumorigenesis, which appears as a potential therapeutic target.