Sirtuin 2 promotes cell stemness and MEK/ERK signaling pathway while reduces chemosensitivity in endometrial cancer
| Autor: | Ping Liu, Nannan Zhao, Yanjuan Guo, Yan Wang, Yan Chen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
MAP Kinase Signaling System
Cell SIRT2 Sirtuin 2 Downregulation and upregulation Cell Line Tumor Medicine Humans Viability assay Cisplatin Mitogen-Activated Protein Kinase Kinases biology business.industry Obstetrics and Gynecology General Medicine Transfection Endometrial Neoplasms medicine.anatomical_structure Cell culture Sirtuin biology.protein Cancer research Female business medicine.drug Signal Transduction |
| Zdroj: | Archives of gynecology and obstetrics. 305(3) |
| ISSN: | 1432-0711 |
| Popis: | Sirtuin 2 (SIRT2) is functionally important in cancer progression and treatment resistance as an NAD+-dependent deacetylase, whereas its role in endometrial cancer (EC) is limitedly investigated. This study aimed to evaluate the regulatory role of SIRT2 on cell stemness and chemosensitivity in EC. SIRT2 expression was detected in human EC cell lines, including Ishikawa, AN3CA, HEC1A, KLE, and normal human endometrial (uterine) epithelial cells (served as controls). Then, SIRT2 overexpression plasmids (constructed with pcDNA3.1 vector) and knock-down plasmids (constructed with pGPH1 vector) were transfected in Ishikawa cells and KLE cells, respectively to assess the influence of SIRT2 on EC cell stemness and chemosensitivity to cisplatin and paclitaxel. SIRT2 mRNA and protein were both overexpressed in EC cell lines (including Ishikawa cells, AN3CA cells, HEC1A cells, and KLE cells) compared with controls. Upregulation of SIRT2 increased the sphere formation capacity (by sphere formation assay and extreme limiting dilution analysis) and CD133+ cells rate in Ishikawa cells, whereas knock-down of SIRT2 reduced the sphere formation capacity and CD133+ cells rate in KLE cells. As for chemosensitivity, upregulation of SIRT2 increased relative cell viability in cisplatin-treated and paclitaxel-treated Ishikawa cells. In contrast, SIRT2 knock-down suppressed relative cell viability in cisplatin-treated but not in paclitaxel-treated KLE cells. In addition, SIRT2 overexpression increased, while SIRT2 knock-down reduced p-MEK and p-ERK1/2 levels in EC cells. SIRT2 promotes cell stemness and activates the MEK/ERK signaling pathway while represses chemosensitivity in EC. |
| Databáze: | OpenAIRE |
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