Abstract: Objective To investigate the role and underlying mechanism of heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) in ferroptosis of human gastric cancer MKN74 cells. Methods Bioinformatic analysis was performed to assess the correlation between HNRNPA1 and ferroptosis-related genes in TCGA gastric cancer dataset. Intracellular Fe²⁺ levels were measured by colorimetric assay, and ROS levels were measured using DCFH-DA fluorescent probe and fluorescence microscopy.Cell viability was determined by CCK-8 assay, and protein expression of SLC7A11 and GPX4 was detected by Western blot. Ferrostatin-1 (Fer-1) was used to inhibit ferroptosis and assess rescue effects. Results Bioinformatic analysis indicated that HNRNPA1 was highly expressed in gastric cancer tissues and positively correlated with SLC7A11. Knockdown of HNRNPA1 significantly increased intracellular Fe²⁺ accumulation and ROS levels, reduced cell viability, and downregulated SLC7A11 and GPX4 expression, while Fer-1 treatment partially reversed these effects. Conclusion HNRNPA1 knockdown promotes ferroptosis in MKN74 cells by downregulating the SLC7A11-GPX4 axis, leading to Fe²⁺ accumulation and ROS elevation. This study elucidates the regulatory role of HNRNPA1 in gastric cancer MKN74 cells ferroptosis and provides experimental evidence for potential HNRNPA1-targeted therapeutic strategies.

Key words: HNRNPA1, gastric cancer, ferroptosis, SLC7A11, GPX4

摘要： 目的 探讨异质性核糖核蛋白A1（HNRNPA1）在胃癌MKN74细胞铁死亡中的作用及机制。方法 通过生物信息学分析TCGA数据库HNRNPA1与铁死亡相关基因的表达相关性;采用比色法检测细胞内亚铁离子（Fe²⁺）水平;采用DCFH-DA荧光探针法检测细胞内活性氧（ROS）水平;CCK-8法测定细胞活力;Western blot法检测谷胱甘肽过氧化物酶4（GPX4）、溶质载体家族7成员11（SLC7A11）蛋白表达水平,并通过Ferrostatin-1（Fer-1）进行铁死亡抑制实验。结果 生信分析显示HNRNPA1在胃癌组织中高表达,并与SLC7A11呈正相关;敲低HNRNPA1可显著增加MKN74细胞Fe²⁺积累和ROS水平,降低细胞活力,同时下调SLC7A11与GPX4蛋白表达,Fer-1处理可部分逆转上述表型。结论 HNRNPA1敲低可通过下调SLC7A11-GPX4轴,促进细胞Fe²⁺积累和ROS水平升高,从而触发铁死亡。本研究揭示HNRNPA1在胃癌MKN74细胞铁死亡中的调控作用,为靶向HNRNPA1的新型治疗策略提供实验依据。

关键词: HNRNPA1, 胃癌, 铁死亡, SLC7A11, GPX4