|Table of Contents|

Impacts of USP7-MDM2-p53 signal axis on proliferation,apoptosis and cell cycle of endometrial carcinoma cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 02
Page:
214-220
Research Field:
Publishing date:

Info

Title:
Impacts of USP7-MDM2-p53 signal axis on proliferation,apoptosis and cell cycle of endometrial carcinoma cells
Author(s):
WEI Wei1; ZHAO Huijuan2; LIU Xiangcui3
1.Department of Obstetrics and Gynecology,Heze Medical College,Shandong Heze 274000,China;2.Department of Gynecology,Affiliated Hospital of Heze Medical College,Shandong Heze 274000,China;3.Department of Gynecology,Peony People's Hospital of Heze,Shandong Heze 274000,China.
Keywords:
ubiquitin-specific protease 7; Mdm2 p53 binding protein homolog (MDM2)-p53 axis; endometrial carcinoma; proliferation; apoptosis; cell cycle
PACS:
R737.33
DOI:
10.3969/j.issn.1672-4992.2024.02.003
Abstract:
Objective:To investigate the impacts of ubiquitin-specific protease 7 (USP7) on the proliferation,apoptosis and cell cycle of endometrial carcinoma cells by regulating the Mdm2 p53 binding protein homolog (MDM2)-p53 axis.Methods:Western blot was applied to detect the expression of USP7 protein in human endometrial carcinoma tissue,paracancerous tissue,human endometrial epithelial cells hEEC and human endometrial carcinoma cell lines Ishikawa,HEC-1-A,KLE.Ishikawa cells were grouped into NC group,P22077 (USP7 inhibitor) group,pcDNA group,pcDNA-MDM2 group,P22077+pcDNA group,and P22077+pcDNA-MDM2 group.The proliferation of Ishikawa cells was detected by CCK-8 and clonogenic assay.The apoptosis and cell cycle of Ishikawa cells were detected by flow cytometry.Western blot was applied to detect the expression of USP7,CyclinD1,cyclin dependent kinase 2 (CDK2),Bcl-2 associated X protein (Bax),MDM2 and p53 protein in Ishikawa cells.Ishikawa cells were treated with RG7388 (MDM2 inhibitor) or PFT-α (p53 inhibitor) and 20 μmol/L P22077 for 48 h to verify the upstream and downstream relationship of USP7-MDM2-p53 signal axis.Results:USP7 protein was highly expressed in endometrial carcinoma tissues and cells,and the highest expression of USP7 protein was found in Ishikawa cells,therefore,Ishikawa cells were selected as the research object.Compared with NC group,the OD450 value of Ishikawa cells,clone formation rate,the numbers of cells in S phase and G2/M phase,the expression of USP7,CyclinD1,CDK2,MDM2 proteins in P22077 group were lower,and the apoptosis rate,the number of cells in G0/G1 phase,the expression of p53 and Bax proteins were higher (P＜0.05).Compared with NC group and pcDNA group,the OD450 value of Ishikawa cells,clone formation rate,the numbers of cells in S phase and G2/M phase,the expression of USP7,CyclinD1,CDK2,MDM2 proteins in pcDNA-MDM2 group were higher,and the apoptosis rate,the number of cells in G0/G1 phase,the expression of p53 and Bax proteins were lower (P＜0.05).Compared with P22077 group and P22077+pcDNA group,the OD450 value of Ishikawa cells,clone formation rate,the numbers of cells in S phase and G2/M phase,the expression of USP7,CyclinD1,CDK2,MDM2 proteins in P22077+pcDNA-MDM2 group were higher,and the apoptosis rate,the number of cells in G0/G1 phase,the expression of p53 and Bax proteins were lower (P＜0.05).p53 was the downstream molecule of USP7-MDM2 pathway.Conclusion:Inhibition of USP7 expression may activate p53 by down-regulating MDM2,thus inhibiting the proliferation of Ishikawa cells,promoting cell apoptosis and cell cycle arrest.

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