Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 21 1 21 Qiong Wei Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China Chun Wang Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China Yi Yang Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China Yuping Li Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China Huan Huang Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China 2025 09 26 2026 01 27 Long noncoding RNA SSTR5 antisense RNA 1 (lncRNA SSTR5-AS1) is increased in a variety of tumors, but its molecular mechanism in ovarian cancer (OC) remains unreported. lncRNA SSTR5-AS1 and signal transducer and activator of transcription 3 (STAT3) expressions in SKOV3 and A2780 cells were interfered (n=3), and the cells were treated with ferroptosis inhibitor Ferrostatin-1. lncRNA SSTR5-AS1 and STAT3 expressions were discovered. The interaction between them was detected by immunoprecipitation assay. The cell malignant progression was evaluated through Transwell and scratch healing assays. Ferroptosis was measured through kits and fluorescent probes; the expression levels of immunosuppressive factors and STAT3/solute carrier family 7 member 11 (SLC7A11) signaling pathway were discovered through Western blot. A transplanted tumor model (n=6 mice per group) was established to evaluate ferroptosis, immunosuppressive factors, and tumor growth in tumor tissues. lncRNA SSTR5-AS1 was up-regulated on OC cells. LncRNA SSTR5-AS1 and STAT3 bind to each other, and knockdown of lncRNA SSTR5-AS1 can reduce p-STAT3/STAT3 and SLC7A11 protein levels (one-way ANOVA). Knocking down lncRNA SSTR5-AS1 and STAT3 suppressed cell viability, migratory rate, and invasive cell number; increased reactive oxygen species (ROS) and Fe2+ levels; and reduced immunosuppressive factors and ferroptosis proteins. Ferrostatin-1 significantly reversed the effect of knockdown of lncRNA SSTR5-AS1 on ferroptosis. In transplanted tumor tissues, downregulation of lncRNA SSTR5-AS1 can reduce tumor size and volume, show obvious iron deposition, and reduce the secretion of immunosuppressive factors. Knockdown of lncRNA SSTR5-AS1 induces ferroptosis and reduces the secretion of immunosuppressive factors through the STAT3/SLC7A11 pathway, thereby antagonizing OC. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4598 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4598/2329