Glucose starvation promotes hnRNPA2B1 cytoplasmic translocation and activates AKT to maintain prostate cancer cell survival

Liangbo SUN; Meng HE; Dong LIU; Fengtian HE; Jiqin LIAN; Mingzhen YANG

doi:10.16016/j.2097-0927.202403068

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Glucose starvation promotes hnRNPA2B1 cytoplasmic translocation and activates AKT to maintain prostate cancer cell survival

Basic Medicine | 更新时间：2026-01-09

- Glucose starvation promotes hnRNPA2B1 cytoplasmic translocation and activates AKT to maintain prostate cancer cell survival
- Journal of Army Medical University Vol. 46, Issue 20, Pages: 2284-2290(2024)
- 作者机构：
  
  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
  2.400038 重庆，陆军军医大学(第三军医大学)基础医学院生物化学与分子生物学教研室
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(32300626);the General Project of Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0318);the Special Project of Science and Technology Innovation Capacity Promotion of Army Medical University(2022XQN05)
- DOI：10.16016/j.2097-0927.202403068
  CLC： R343.23;R730.23;R737.25
- Received：14 March 2024，
  
  Revised：2024-05-30，
  
  Published：30 October 2024
- 稿件说明：
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Liangbo SUN, Meng HE, Dong LIU, et al. Glucose starvation promotes hnRNPA2B1 cytoplasmic translocation and activates AKT to maintain prostate cancer cell survival[J]. Journal of Army Medical University, 2024, 46(20): 2284-2290.
DOI：

Liangbo SUN, Meng HE, Dong LIU, et al. Glucose starvation promotes hnRNPA2B1 cytoplasmic translocation and activates AKT to maintain prostate cancer cell survival[J]. Journal of Army Medical University, 2024, 46(20): 2284-2290. DOI： 10.16016/j.2097-0927.202403068.

摘要

目的

探讨葡萄糖饥饿后介导核不均一核糖核蛋白A2B1(heterogeneous nuclear ribonucleoprotein A2B1，hnRNPA2B1)向细胞质转位的分子机制及hnRNPA2B1细胞质转位增加对前列腺癌PC3细胞存活的影响。

方法

前列腺癌PC3细胞株在含葡萄糖的正常1640培养基中常规培养(正常组)，在不含葡萄糖的1640培养基中培养构建葡萄糖饥饿模型(饥饿组)。2组分别进行不同处理：去乙酰化酶抑制剂曲古抑菌素A(trichostatin A，TSA)联合尼克酰胺(nicotinamide，NAM)处理(TSA/NAM组)、AKT抑制剂BEZ235处理、si-NC转染和si-hnRNPA2B1转染。采用细胞质和细胞核蛋白分离技术、免疫沉淀联合Western blot实验检测hnRNPA2B1乙酰化(acetylation，Ac)水平、AKT总蛋白及其磷酸化水平、细胞质和细胞核中hnRNPA2B1的表达水平；采用CCK-8检测各组细胞存活情况。

结果

与正常组比较，在葡萄糖饥饿处理3~5 h后，PC3细胞hnRNPA2B1蛋白乙酰化降低(

＜0.01)，其细胞质转位增加(

＜0.01)，AKT磷酸化增强促进AKT信号通路的激活；与饥饿组比较，使用TSA/NAM、BEZ235和转染si-hnRNPA2B1处理后hnRNPA2B1乙酰化水平明显上调(

＜0.01)，能够抑制葡萄糖饥饿介导的hnRNPA2B1细胞质转位、抑制AKT磷酸化，同时导致葡萄糖饥饿处理后的细胞存活率进一步降低(

＜0.01)。

结论

葡萄糖饥饿环境通过诱导Ac-hnRNPA2B1-AKT信号通路激活，从而维持PC3细胞存活。

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 (

0.01)

and its cytoplasmic translocation was increased in PC3 cells (

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 (

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 (

0.01).

Conclusion

Glucose starvation can maintain the survival of PC3 cells by inducing the activation of the Ac-hnRNPA2B1-AKT signaling pathway.

关键词

Keywords

references

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