SENP1 induced protein deSUMO modification increased the chemotherapy sensitivity of endometrial cancer side population cells.
10.3760/cma.j.cn112152-20201108-00968
- Author:
Meng Lan YUAN
1
;
Jie BAI
2
;
Cheng Yao LI
2
;
Na XUE
3
;
Xu Hong CHEN
1
;
Feng SHENG
4
;
Xiao Zhi LIU
3
;
Pu LI
2
Author Information
1. Department of Obstetrics and Gynecology, Tianjin Fifth Central Hospital, Tianjin 300450, China.
2. Department of Obstetrics and Gynecology, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300052, China.
3. Tianjin Key Laboratory of Epigenetics in Organ Development of Premature Infants, Tianjin 300450, China.
4. Department of Traditional Chinese Medicine, Tianjin Fifth Central Hospital, Tianjin 300450, China.
- Publication Type:Journal Article
- Keywords:
Cisplatin;
Endometrial neoplasms;
Sentrin/SUMO-specific proteases 1;
Small ubiquitin-related modifier;
Tumor side population cells
- MeSH:
Animals;
Female;
Humans;
Mice;
Apoptosis;
Cell Line, Tumor;
Cisplatin/pharmacology*;
Cysteine Endopeptidases/metabolism*;
Endometrial Neoplasms/genetics*;
Side-Population Cells/pathology*;
Sumoylation
- From:
Chinese Journal of Oncology
2022;44(12):1362-1368
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To inhibit the stemness maintenance potential of endometrial cancer and increase the sensitivity of endometrial cancer side population cells to chemotherapy drugs by inducing extensive deSUMOylation modification of proteins. Methods: Flow cytometry was used to sort and culture CD133(+) CD44(+) KLE endometrial cancer cell clone spheres. Protein expression level of small ubiquitin-related modifier 1 (SUMO1) and two stemness maintenance genes of tumor side population cells, octamer binding transcription factor-4 (Oct4) and sex determining region Y-box2 (Sox2), were detected by western blotting method. Lentivirus-mediated Sentrin/SUMO-specific proteases 1 (SENP1) gene was stably transfected into KLE side population cells. Western blotting was used to detect the protein expressions of SENP1, SUMO1, Oct4 and Sox2. The clone formation rate was compared between KLE side population cells with or without SENP1 overexpression. Flow cytometry was applied to detect cell cycle changes. 3-(4, 5-Dimethylthiazole-2)-2, 5-diphenyl-tetrazolium bromide (MTT) experiment and flow cytometry apoptosis method were used to detect the chemosensitivity of the side population of endometrial cancer cells to cisplatin. Tumor-bearing mouse models of endometrial cancer were established to detect the effect of SENP1 overexpression on the chemotherapy sensitivity of cisplatin. Results: Compared with CD133(-)CD44(-) KLE cells, CD133(+) CD44(+) KLE side population cells could form clonal spheres and express higher levels of SUMO1, Oct4 and Sox2 proteins (P<0.05). Compared with KLE side population cells that were not transfected with SENP1 gene, the expression level of SENP1 protein in KLE side population cells overexpressing SUMO1、Oct4 and Sox2 were lower. The clonal sphere formation rate was reduced from (25.67±5.44)% to (7.46±1.42)%, and cell cycle shifted from G(0)/G(1) phase to G(2) phase. IC(50) of cisplatin decreased from (55.46±6.14) μg/ml to (11.55±3.12) μg/ml, and cell apoptosis rate increased from (9.76±2.09)% to (16.79±3.44)%. Overexpression of SENP1 could reduce the tumorigenesis rate of KLE side population cells in vivo and increase their chemotherapy sensitivity to cisplatin (P<0.05). Conclusion: Overexpression of SENP1 can induce protein deSUMOylation modification, inhibit the stemness maintenance potential of endometrial cancer side population cells, and enhance their chemotherapy sensitivity, which provides a new reference for gene therapy of endometrial cancer.
