Circular RNA circPRKCA represses ferroptosis of hepatocellular carcinoma by promoting SLC7A11

Circular RNAs are widely recognized as pivotal regulators of cancer development, and ferroptosis --a unique iron-dependent cell death mechanism driven by the accumulation of lipid peroxides --has emerged as a crucial process in oncobiology. This study aimed to elucidate the functional significance of circPRKCA in modulating ferroptosis in hepatocellular carcinoma (HCC). The expression profiles of circPRKCA in HCC tissues obtained from patients via surgical resection, paired adjacent non-tumorous tissues, and HCC cell lines were quantified using qRT-PCR, while its subcellular localization was determined through fluorescence in situ hybridization (FISH). To explore its functional relevance, circPRKCA was knocked down in HCC cells using small interfering RNA (siRNA), with cellular viability and invasiveness assessed via CCK-8 and Transwell assays, respectively. Ferroptosis progression was evaluated by quantifying ferroptosis-related biomarkers, including total iron content, labile iron pool (Fe2⁺), and lipid reactive oxygen species (ROS). Additionally, an in vivo xenograft mouse model was established to verify the effects of circPRKCA, and bioinformatics analysis combined with dual-luciferase reporter assays was used to identify its interacting molecules. Results showed that circPRKCA is significantly upregulated in HCC; knockdown of circPRKCA induces ferroptosis, suppresses proliferation in HCC cells, and inhibits HCC tumor growth.
Furthermore, circPRKCA targets miR-384 to regulate SLC7A11 expression, thereby modulating ferroptosis in HCC cells via the miR-384/SLC7A11 axis.