Downregulation of HULC Induces Ferroptosis in Hepatocellular Carcinoma via Targeting of the miR-3200-5p/ATF4 Axis

Abstract

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.