SETDB1 regulates cell senescence through p53/p21 signaling
10.19405/j.cnki.issn1000-1492.2022.09.019
- Author:
Qian Wu
1
;
Jixue Hou
1
;
Qiang He
1
;
Xiaobin Cui
2
;
Guilin Huang
1
;
Xuling Sun
1
Author Information
1. Dept of Gastrointestinal and Breast Surgery, The First Afiliated Hospital of Medical College of Shihezi University,Shihezi 832008
2. Dept ofPathology,School of Medicine ,Shihezi University,Shihezi 832008
- Publication Type:Journal Article
- Keywords:
colon cancer;
SETDB1;
cell proliferation;
cellular senescence;
p53
- From:
Acta Universitatis Medicinalis Anhui
2022;57(9):1442-1446,1452
- CountryChina
- Language:Chinese
-
Abstract:
Objective : To investigate the effects of SETDB1 on the proliferation and apoptosis of human colon cancer cells.
Methods :The senescence of colon cancer cells was induced by doxorubicin, and the protein expression of SETDB1 in the senescent cells was detected by Western blot.Colon cancer cell models with low expression of SETDB1 and overexpression of SETDB1 were constructed by using shRNA(shSETDB1#1 and shSETDB1#2) of SETDB1 and overexpression plasmid, respectively.Western blot was used to detect the expression of SETDB1,the CCK8 assay was performed to detect cell proliferation while a Senescence β-Galactosidase Staining Kit was used to detect senescent cells, and Western blot was used to detect the changes of p53 and p21.The reverse experiment was carried out with p53 overexpression plasmid.
Results :Cell senescence evoked by doxorubicin could down-regulate the protein expression of SETDB1.After low expression of SETDB1,the proliferation ability of colonic cancer cells decreased, and the proportion of senescent cells increased from(22.00±4.35)% to(54.00±5.56)% and(53.33±4.93)%(P<0.001).After overexpression of STEDB1,the proliferation ability of colon cancer cells increased, and the ratio of senescent cells decreased from(43.33±6.11)% to(21.33±3.51)%(P<0.01).Through GSE56496 enrichment and analysis, it was found that SETDB1 was related to p53 signal pathway, silencing SETDB1 could increase the levels of p53 and p21 protein, while overexpression of SETDB1 could decrease the level of p53 and p21 protein, and overexpression of p53 reversed the decrease of cell senescence caused by overexpression of SETDB1.
Conclusion :SETDB1 inhibits the senescence of colon cancer cells by inhibiting p53/p21 signal pathway, which provides a potential target for individualized tumor therapy.
- Full text:2024122711084275396SETDB1通过p53_p21通路调控结肠癌细胞衰老_吴倩.pdf
