Ywhab inhibits growth of mouse B-cell lymphoma 38B9 cells by targeting HSP90aa1
10.3969/j.issn.1000-4718.2024.03.002
- VernacularTitle:Ywhab通过靶向Hsp90aa1抑制小鼠B细胞淋巴瘤38B9细胞生长
- Author:
Zichen WEI
1
;
Yi ZHANG
;
Han XU
;
Xin WANG
;
Ting GU
;
Lei PANG
;
Mingchao ZHAO
;
Duonan YU
Author Information
1. 扬州大学医学院/江苏省非编码RNA基础与临床转化重点实验室,江苏 扬州 225009
- Keywords:
Ywhab gene;
14-3-3β protein;
diffuse large B-cell lymphoma;
38B9 cells;
apoptosis;
Hsp90aa1 protein
- From:
Chinese Journal of Pathophysiology
2024;40(3):395-403
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the role of Ywhab in the growth of mouse B-cell lymphoma,and to explore the potential underlying mechanisms.METHODS:The correlation between Ywhab and human diffuse large B-cell lymphoma(DLBCL)was investigated by bioinformatics analysis.Infection with retroviral vector was performed to establish stable mouse B-cell lymphoma 38B9 cell line with overexpression of Ywhab gene,which was verified by RT-qPCR and Western blot.The impact of Ywhab overexpression on 38B9 cell growth both in vitro and in vivo was detected by cell counting,CCK-8 assay,and subcutaneous tumor loading experiments.The expression of apoptosis-related proteins was detected by RT-qPCR and Western blot.Co-immunoprecipitation combined with mass spectrometry(CoIP-MS)was employed to search for proteins specifically binding to Ywhab gene product 14-3-3β,which was confirmed by Western blot and molecu-lar docking analysis.RESULTS:The Ywhab gene exhibited low expression in DLBCL,which was correlated with poor clinical prognosis of DLBCL patients.Compared with normal mouse bone marrow B cells,Ywhab expression was low in 38B9 cells.Overexpression of Ywhab induced apoptosis of 38B9 cells both in vitro and in vivo,promoted the expression of pro-apoptotic proteins Puma,Noxa and Bax at both mRNA and protein levels,and inhibited the mRNA and protein expres-sion of anti-apoptotic protein Bcl2(P＜0.05).The 14-3-3β protein specifically bound to Hsp90aa1 and reduced Hsp90aa1 protein levels,thereby suppressing the growth of 38B9 cells.CONCLUSION:Ywhab promotes the apoptosis of B-cell lymphoma cells by binding to Hsp90aa1 and thereby inhibiting the function of Hsp90aa1.
