Targeting Oncogenic lncRNA KRT7-AS to Induce Ferroptosis Suppresses Ovarian Cancer Progression

Ovarian cancer poses the greatest threat to survival among gynecologic cancers in women. Long non-coding RNAs (lncRNAs) have emerged as critical regulators in oncogenesis. The current study aimed to elucidate the function and regulatory mechanism of lncRNA KRT7-AS in ovarian cancer.

The clinical significance of KRT7-AS was evaluated through bioinformatics analysis of data from public repositories. KRT7-AS expression was examined by RT-qPCR and fluorescence in situ hybridization. The function analyses were conducted using assays for cell proliferation, migration, invasion, wound healing, and colony formation. Assessment of cell cycle and apoptosis was performed using flow cytometry. Mitochondrial membrane potential (MMP), reactive oxygen species (ROS), lipid peroxidation, and ferrous iron (Fe²⁺) levels were measured with specific kits. Tumor growth was assessed using a xenograft mouse model.

Patients exhibiting high KRT7-AS expression had a significantly lower survival rate. Functional assays demonstrated that KRT7-AS overexpression enhanced tumorigenic behaviors, including cell proliferation, invasion, and metastasis, whereas its knockdown suppressed these malignant phenotypes. KRT7-AS depletion induced ferroptosis, as indicated by increased MMP and ROS levels, and the accumulation of lipid peroxidation and Fe²⁺. In rescue experiments, the ferroptosis inhibitor ferrostatin-1 reversed the reduction in cell viability caused by KRT7-AS knockdown. Finally, in vivo studies showed that KRT7-AS knockdown inhibited tumor growth and modulated the expression of ferroptosis-related proteins by elevating ACSL4 and reducing GPX4.

These findings suggest that KRT7-AS has potential as a diagnostic biomarker for ovarian cancer. Targeting KRT7-AS to induce ferroptosis may represent a promising therapeutic strategy for suppressing ovarian cancer progression.