Medical Research Center, Henan International Joint Laboratory of Thrombosis and Hemostasis, School of Basic Medicine, Henan University of Science and Technology, Luoyang 471000, China.
Department of Geriatric Medicine, Jiaozuo People's Hospital, Xinxiang Medical University, Jiaozuo 454000, China.
Oxid Med Cell Longev. 2022 May 16;2022:9613095. doi: 10.1155/2022/9613095. eCollection 2022.
Hepatocellular carcinoma is a malignant tumor that poses a serious threat to human health. Ferroptosis, which represents an identified type of regulated iron-dependent cell death, may play an important role in hepatocellular carcinoma. However, it is unclear as to whether ferroptosis is involved with the mechanisms of lncRNA HULC in liver cancer cells. Here, we show that knockdown of HULC increases ferroptosis and oxidative stress in liver cancer cells. We also found changes in some related miRNAs in cells treated with HULC siRNA. Differential miRNA expression levels were determined with the use of high-throughput sequencing and prediction target genes identified using bioinformatics analysis. HULC was found to function as a ceRNA of miR-3200-5p, and miR-3200-5p regulates ferroptosis by targeting ATF4, resulting in the inhibition of proliferation and metastasis within HCC cells. In summary, these findings illuminate some of the molecular mechanisms through which downregulation of HULC induces liver cancer cell ferroptosis by targeting the miR-3200-5p/ATF4 axis to modulate the development of hepatocellular carcinoma.
肝细胞癌是一种严重威胁人类健康的恶性肿瘤。铁死亡作为一种明确的受调控的铁依赖性细胞死亡方式，可能在肝细胞癌中发挥重要作用。然而，lncRNA HULC 在肝癌细胞中的作用机制是否与铁死亡有关尚不清楚。在这里，我们发现 HULC 的敲低会增加肝癌细胞中的铁死亡和氧化应激。我们还发现，用 HULC siRNA 处理的细胞中一些相关 miRNA 发生了变化。使用高通量测序确定了差异 miRNA 的表达水平，并通过生物信息学分析预测了靶基因。发现 HULC 作为 miR-3200-5p 的 ceRNA，miR-3200-5p 通过靶向 ATF4 调节铁死亡，从而抑制 HCC 细胞的增殖和转移。总之，这些发现阐明了一些分子机制，即下调 HULC 通过靶向 miR-3200-5p/ATF4 轴抑制铁死亡，从而调节肝细胞癌的发生发展。
