Inhibition of circRNA NGFR promotes ferroptosis in gallbladder carcinoma cells.

ABSTRACT

Background: Gallbladder carcinoma (GBC) is a formidably aggressive malignancy. Circular RNAs (circRNAs) play crucial regulatory roles in cancer. NGFR is a novel circRNA implicated in various types of cancers. The primary goal of this study was to elucidate the role of NGFR in GBC. Methods: NGFR variants exhibiting discernible discrepancies were identified using RNA sequencing and validated using real-time PCR. Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine and Cell Counting Kit-8 assays. The ferroptotic phenotype was characterized by assessing the reactive oxygen species and Fe2+ levels. Western blotting was used to analyze ferroptosis-associated proteins. Superoxide dismutase, malondialdehyde, and glutathione levels were measured using commercially available reagent kits. The severity of mitochondrial damage was evaluated by assessing JC-1, MitoSOX, and ATP activities. Results: NGFR was upregulated, and its suppression inhibited cell proliferation and increased Fe2+ levels in GBC cells. Furthermore, NGFR downregulation disrupted mitochondrial function. Conclusion: Circular RNA NGFR can impede the advancement of GBC by modulating the ferroptotic phenotype, thereby potentially offering a novel avenue for the clinical diagnosis and treatment strategies of GBC.