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lnc-POTEG-4调控miR-498/AR表达抑制食管鳞状细胞癌铁死亡的发生
作者:米彩锋1  赵武斌2  李亚利1  余儒桓1  杨洋3 
单位:1. 平顶山学院第一附属医院 消化内科, 河南 平顶山 467000;
2. 平顶山学院第一附属医院 医教部, 河南 平顶山 467000;
3. 郑州大学第一附属医院 胸外科, 河南 郑州 450052
关键词:lnc-POTEG-4 miR-498 雄激素受体 食管鳞状细胞癌 铁死亡 
分类号:R735.1
出版年·卷·期(页码):2022·41·第五期(597-609)
摘要:

目的:探讨lnc-POTEG-4/miR-498/AR对食管鳞状细胞癌(ESCC)铁死亡的调节作用,并阐明其作用机制。方法:采用qRT-PCR检测lnc-POTEG-4、miR-498和AR的表达。用CCK-8或流式细胞仪检测细胞存活或凋亡,分别用C11-BODIP染色法和铁试剂盒分析细胞内脂质活性氧(ROS)、丙二醛(MDA)和Fe2+的积累。双荧光素酶报告实验用于验证miR-498与lnc-POTEG-4或AR的相互作用关系。结果:在ESCC中,lnc-POTEG-4和AR表达升高,miR-498表达降低。沉默lnc-POTEG-4可促进ESCC细胞铁死亡。miR-498是lnc-POTEG-4的靶点,且与AR直接相互作用,lnc-POTEG-4作为miR-498的海绵调控AR在ESCC中的表达,抑制miR-498或过表达AR可以部分减轻lnc-POTEG-4缺失引起的细胞铁死亡。结论:lnc-POTEG-4通过调节miR-498/AR表达抑制ESCC铁死亡的发生。我们的发现为增加Erastin诱导的ESCC细胞铁死亡提供了新的策略。

Objective: To investigate the regulatory effects of lnc-POTEG-4/miR-498/AR on ferroptosis in esophageal squamous cell carcinoma(ESCC), and to clarify its mechanism. Methods: The expressions of lnc-POTEG-4, miR-498 and AR were detected by qRT-PCR. Cell survival or apoptosis was detected by CCK-8 or flow cytometry, and the accumulation of intracellular lipid reactive oxygen species(ROS), malondialdehyde(MDA) and Fe2+ was analyzed by C11-BODIP staining and iron kit, respectively. The dual-luciferase reporter assay was used to verify the interaction between miR-498 and lnc-POTEG-4 or AR. Results: In ESCC, the expressions of lnc-POTEG-4 and AR were increased, and the expression of miR-498 was decreased. Silencing of lnc-POTEG-4 promoted ferroptosis in ESCC cells. miR-498 was the target of lnc-POTEG-4 and directly interacted with AR. lnc-POTEG-4 acted as a sponge of miR-498 to regulate AR expression in ESCC, and inhibition of miR-498 or overexpression of AR could partially alleviate cell ferroptosis induced by lnc-POTEG-4 deletion. Conclusion: lnc-POTEG-4 inhibits ferroptosis in ESCC by regulating the miR-498/AR expression. Our findings provide a new strategy for enhancing Erastin-induced ferroptosis in ESCC cells.

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