The role and mechanism of TENT5B in upregulating PRKAA2 expression to promote ferroptosis in gastric cancer
10.7659/j.issn.1005-6947.250323
- VernacularTitle:TENT5B上调PRKAA2表达促进胃癌铁死亡的作用与机制研究
- Author:
Zhi LIN
1
;
Liang LI
;
Kaiyu ZHU
;
Fei LONG
Author Information
1. 中南大学湘雅三医院儿科,湖南 长沙 410013
- Publication Type:Journal Article
- Keywords:
Stomach Neoplasms;
Ferroptosis;
DNA Nucleotidylexotransferase;
AMP-Activated Protein Kinases
- From:
Chinese Journal of General Surgery
2025;34(9):1975-1986
- CountryChina
- Language:Chinese
-
Abstract:
Background and Aims:Gastric cancer remains a common malignancy worldwide with a poor prognosis and limited response to current therapies.Ferroptosis,a novel form of regulated cell death,has emerged as a promising therapeutic target in cancer.Terminal nucleotidyltransferase 5B(TENT5B)is downregulated in various tumors,but its role in gastric cancer and ferroptosis remains unclear.This study aimed to investigate the expression pattern and biological function of TENT5B in gastric cancer and to elucidate its underlying mechanisms in regulating ferroptosis.Methods:The expression of TENT5B in gastric cancer was analyzed using TCGA and GEO datasets,and further validated in gastric cancer tissues and cell lines by qRT-PCR and Western blotting.CCK-8,colony formation,wound healing,and Transwell assays were performed to evaluate the effects of TENT5B overexpression on cell proliferation and migration.Ferroptosis was assessed by measuring cell viability,lipid ROS,and MDA levels.Bioinformatics analysis,mRNA stability assays,and rescue experiments were conducted to explore the molecular mechanisms.A subcutaneous xenograft mouse model was used to validate the in vivo effects.Results:TENT5B was significantly downregulated in gastric cancer tissues and cells.Overexpression of TENT5B inhibited cell proliferation and migration while promoting ferroptosis.Mechanistically,TENT5B enhanced PRKAA2 mRNA stability and upregulated its expression,thereby exerting tumor-suppressive effects.In vivo,TENT5B overexpression suppressed tumor growth and elevated PRKAA2 expression.Conclusion:TENT5B functions as a tumor suppressor in gastric cancer by stabilizing PRKAA2 mRNA,promoting ferroptosis,and inhibiting cancer progression.These findings suggest that TENT5B may serve as a promising molecular target for ferroptosis-based therapeutic strategies in gastric cancer.
