Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Cell Death Dis. 2022 Aug 25;13(8):734. doi: 10.1038/s41419-022-05173-1.
Ferroptosis is a new type of cell death that has been recognized in recent years and is different from apoptosis, autophagy, and necrosis. It is mainly due to cellular iron homeostasis and lipid peroxidation of iron metabolism caused by large accumulation. There is a close correlation between ferroptosis and hepatocellular carcinoma (HCC). This study shows that the expression of the long noncoding RNA HEPFAL was reduced in HCC tissues. We found that lncRNA HEPFAL can promote ferroptosis by reducing the expression of solute carrier family 7 member 11 (SLC7A11) and increasing the levels of lipid reactive oxygen species (ROS) and iron (two surrogate markers of ferroptosis). In addition, we found that lncRNA HEPFAL increases the sensitivity of erastin-induced ferroptosis, which may be related to mTORC1, and lncRNA HEPFAL can promote the ubiquitination of SLC7A11 and reduce the stability of the SLC7A11 protein, resulting in decreased expression. Understanding these mechanisms indicates that lncRNAs related to ferroptosis are essential for the occurrence and treatment of HCC.
铁死亡是近年来新发现的一种细胞死亡方式，与细胞凋亡、自噬和坏死不同。它主要是由于细胞内铁稳态和铁代谢的脂质过氧化作用导致大量积累。铁死亡与肝细胞癌（HCC）密切相关。本研究表明，长链非编码 RNA HEPFAL 在 HCC 组织中的表达降低。我们发现，lncRNA HEPFAL 可以通过降低溶质载体家族 7 成员 11（SLC7A11）的表达和增加脂质活性氧（ROS）和铁（铁死亡的两个替代标志物）的水平来促进铁死亡。此外，我们发现 lncRNA HEPFAL 增加了依马替尼诱导的铁死亡的敏感性，这可能与 mTORC1 有关，lncRNA HEPFAL 可以促进 SLC7A11 的泛素化，降低 SLC7A11 蛋白的稳定性，导致表达减少。了解这些机制表明，与铁死亡相关的 lncRNAs 是 HCC 发生和治疗的关键。
