Glucose starvation promotes hnRNPA2B1 cytoplasmic translocation and activates AKT to maintain prostate cancer cell survival
10.16016/j.2097-0927.202403068
- VernacularTitle:葡萄糖饥饿促进hnRNPA2B1细胞质转位并激活AKT维持前列腺癌细胞存活
- Author:
Liangbo SUN
1
;
Meng HE
;
Dong LIU
;
Fengtian HE
;
Jiqin LIAN
;
Mingzhen YANG
Author Information
1. 400038 重庆,陆军军医大学(第三军医大学)药学与检验医学系临床生物化学教研室
- Keywords:
glucose starvation;
prostate cancer;
hnRNPA2B1;
acetylation;
AKT signal
- From:
Journal of Army Medical University
2024;46(20):2284-2290
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the molecular mechanism of translocation of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1 )to the cytoplasm after glucose starvation and the effects of increased cytoplasmic translocation of hnRNPA2B1 on the survival of prostate cancer PC3 cells. Methods Human prostate cancer PC3 cells were divided into normal control group (cultured conventionally with glucose-containing medium,RPMI 1640 Medium)and glucose starvation group (cultured with glucose-free medium,RPMI 1640 Medium).The 2 types of cells were treated with deacetylase inhibitor,trichostatin A (TSA ) combined with nicotinamide (NAM),AKT inhibitor BEZ235,si-NC transfection,and si-hnRNPA2B1 transfection,respectively.Cytoplasmic and nuclear protein separation,immunoprecipitation and Western blotting were used to detect changes in hnRNPA2B1 acetylation,total AKT protein and its phosphorylation level,and expression levels of hnRNPA2B1 in the cytoplasm and nucleus.CCK-8 assay was employed to observe cell survival in each group.Results After 3～5 h of glucose starvation treatment,the acetylation of hnRNPA2B1 protein was reduced (P<0.01 ),and its cytoplasmic translocation was increased in PC3 cells (P<0.01 ),which was accompanied by enhanced AKT phosphorylation and activation of the AKT signaling pathway.TSA/NAM treatment,BEZ235 treatment,and si-hnRNPA2B1 transfection all resulted in obvious increase in acetylation of hnRNPA2B1 protein when compared with glucose starvation treated cells (P<0.01 ),which could inhibit the glucose starvation-mediated cytoplasmic translocation of hnRNPA2B1,suppress AKT phosphorylation,and consequently decrease the cell survival rate after glucose starvation (P<0.01).Conclusion Glucose starvation can maintain the survival of PC3 cells by inducing the activation of the Ac-hnRNPA2B1-AKT signaling pathway.
