Tanshinone IIA destabilizes SLC7A11 by regulating PIAS4-mediated SUMOylation of SLC7A11 through KDM1A, and promotes ferroptosis in breast cancer

• DOI: 10.1016/j.jare.2024.04.009
• Publication Date: 2024-04-12T06:13:02Z
• Authors: Na Luo; KeJing Zhang; Xin Li; Yu Hu; Lei Guo

Breast cancer (BC) is the most common malignancy in women with unfavorite prognosis. Tanshinone IIA (Tan IIA) inhibits BC progression, however, underlying mechanism remains largely undefined. The cytotoxicity of Tan was assessed by CCK-8 and LDH assays. Ferroptosis monitored level MDA, Fe2+, lipid ROS GSH. IHC western blot were employed to detect localization expression SLC7A11, PIAS4, KDM1A other key molecules. SUMOylation SLC7A11 detected Ni-beads pull-down assay co-IP. Luciferase ChIP assays direct association between PIAS4 promoter. proliferative metastatic properties cells colony formation, Transwell assays, respectively. vitro findings verified xenograft lung metastasis models. promoted ferroptosis suppressing cells. Silencing or inhibited cell growth BC. Mechanistically, facilitated via binding acted as a transcriptional activator PIAS4. Functional studies further revealed that decreased expression, thus transcriptionally. inhibition PIAS4-dependent induced ferroptosis, thereby inhibiting proliferation tumor KDM1A/PIAS4/SLC7A11 axis.