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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
Glucose starvation promotes hnRNPA2B1 cytoplasmic translocation and activates AKT to maintain prostate cancer cell survival
- 陆军军医大学学报 2024年46卷第20期 页码：2284-2290
- 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：
[杨明珍，E-mail：yangmingzhen0807@126.com YANG Mingzhen, E-mail: yangmingzhen0807@126.com
- 基金信息：国家自然科学基金青年科学基金项目(32300626);重庆市自然科学基金面上项目(cstc2021jcyj-msxmX0318);陆军军医大学科技创新能力提升专项项目(2022XQN05)
DOI：10.16016/j.2097-0927.202403068
中图分类号： R343.23;R730.23;R737.25收稿：2024-03-14，
修回：2024-05-30，
纸质出版：2024-10-30
- 稿件说明：
移动端阅览
孙梁博, 贺梦, 刘冬, 等. 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[J]. 陆军军医大学学报, 2024,46(20):2284-2290.
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.
孙梁博, 贺梦, 刘冬, 等. 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[J]. 陆军军医大学学报, 2024,46(20):2284-2290. DOI： 10.16016/j.2097-0927.202403068.
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
2
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
2
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
2
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(
P
＜0.01)，其细胞质转位增加(
P
＜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(
P
＜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(
P
＜0.01)。
结论
2
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
2
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
2
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
2
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
2
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
SIEGEL R L, GIAQUINTO A N, JEMAL A. Cancer statistics, 2024[J]. CA Cancer J Clin, 2024, 74(1): 12-49. DOI: 10.3322/caac.21820.
WASIM S, LEE S Y, KIM J. Complexities of prostate cancer[J]. Int J Mol Sci, 2022, 23(22): 14257. DOI: 10.3390/ijms232214257.
WAWRZKIEWICZ-JAŁOWIECKA A, LALIK A, LUKASIAK A, et al . Potassium channels, glucose metabolism and glycosylation in cancer cells[J ] . Int J Mol Sci, 2023, 24(9): 7942. DOI: 10.3390/ijms24097942.
ABDEL-WAHAB A F, MAHMOUD W, AL-HARIZY R M. Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy[J]. Pharmacol Res, 2019, 150: 104511. DOI: 10.1016/j.phrs.2019.104511.
OAKES S A. Endoplasmic reticulum stress signaling in cancer cells[J]. Am J Pathol, 2020, 190(5): 934-946. DOI: 10.1016/j.ajpath.2020.01.010.
CUI Y N, SUN Y L, LI D M, et al . The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade[J ] . Front Cell Dev Biol, 2023, 11: 1275543. DOI: 10.3389/fcell.2023.1275543.
PETRI B J, PIELL K M, SOUTHWHITT G C, et al . HNRNPA2B1 regulates tamoxifen-and fulvestrant-sensitivity and hallmarks of endocrine resistance in breast cancer cells[J ] . Cancer Lett, 2021, 518: 152-168. DOI: 10.1016/j.canlet.2021.07.015.
TAKAHASHI T, ANDO Y, ICHIKAWA H, et al . Serum/glucose starvation strikingly reduces heterogeneous nuclear ribonucleoprotein A1 protein and its target, cyclin D1[J ] . FEBS J, 2023, 290(16): 4126-4144. DOI: 10.1111/febs.16802.
MARTÍNEZ-REYES I, CHANDEL N S. Cancer metabolism: looking forward[J]. Nat Rev Cancer, 2021, 21(10): 669-680. DOI: 10.1038/s41568-021-00378-6.
WANG G L, ZHANG X F, CHENG W, et al . CHD1L prevents lipopolysaccharide-induced hepatocellular carcinomar cell death by activating hnRNP A2/B1-nmMYLK axis[J ] . Cell Death Dis, 2021, 12(10): 891. DOI: 10.1038/s41419-021-04167-9.
GUO Q D, FAN Y, WANG Q T, et al . Glioblastoma upregulates SUMOylation of hnRNP A2/B1 to eliminate the tumor suppressor miR-204-3p, accelerating angiogenesis under hypoxia[J ] . Cell Death Dis, 2023, 14(2): 147. DOI: 10.1038/s41419-023-05663-w.
LIU H, LI D X, SUN L N, et al . Interaction of lncRNA MIR100HG with hnRNPA2B1 facilitates m 6 A-dependent stabilization of TCF7L2 mRNA and colorectal cancer progression[J ] . Mol Cancer, 2022, 21(1): 74. DOI: 10.1186/s12943-022-01555-3..
QI F, SHEN W Y, WEI X Y, et al . CSNK1D-mediated phosphorylation of HNRNPA2B1 induces miR-25-3p/miR-93-5p maturation to promote prostate cancer cell proliferation and migration through m 6 A-dependent manner[J ] . Cell Mol Life Sci, 2023, 80(6): 156. DOI: 10.1007/s00018-023-04798-5..
KIM M K, CHOI M J, LEE H M, et al . Heterogeneous nuclear ribonucleoprotein A2/B1 regulates the ERK and p53/HDM2 signaling pathways to promote the survival, proliferation and migration of non-small cell lung cancer cells[J ] . Oncol Rep, 2021, 46(2): 153. DOI: 10.3892/or.2021.8104.
GAO L B, ZHU X L, SHI J X, et al . HnRNPA2B1 promotes the proliferation of breast cancer MCF-7 cells via the STAT3 pathway[J ] . J Cell Biochem, 2021, 122(3/4): 472-484. DOI: 10.1002/jcb.29875.
CUI H Q, WU F, SUN Y L, et al . Up-regulation and subcellular localization of hnRNP A2/B1 in the development of hepatocellular carcinoma[J ] . BMC Cancer, 2010, 10: 356. DOI: 10.1186/1471-2407-10-356.
NARITA T, WEINERT B T, CHOUDHARY C. Functions and mechanisms of non-histone protein acetylation[J]. Nat Rev Mol Cell Biol, 2019, 20(3): 156-174. DOI: 10.1038/s41580-018-0081-3.
INUZUKA H, GAO D M, FINLEY L W S, et al . Acetylation-dependent regulation of Skp2 function[J ] . Cell, 2012, 150(1): 179-193. DOI: 10.1016/j.cell.2012.05.038.
LI Y P, HE X N, LU X, et al . METTL3 acetylation impedes cancer metastasis via fine-tuning its nuclear and cytosolic functions[J ] . Nat Commun, 2022, 13(1): 6350. DOI: 10.1038/s41467-022-34209-5.
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