PPP2R2B targets the JAK2-STAT3 signaling pathway to regulate ferroptosis in breast cancer cells.

Abstract

We aimed to explore the effect and the mechanism of PPP2R2B on cell proliferation, migration, and ferroptosis in breast cancer cells. By bioinformatic analysis and data mining, PPP2R2B was associated with the prognosis and ferroptosis of breast cancer. Breast cancer cells were transfected with PPP2R2B overexpression or PPP2R2B knockdown plasmids, and cell proliferation, apoptosis, migration, and invasion were examined. Moreover, transfected breast cancer cells were treated with ferroptosis inducer, and the relative iron level, Fe²⁺ level, MDA level, lipid ROS level, MitoSOX intensity, and fluorescence intensity were detected. Protein expressions of GPX4, ACSL4, and SLC7A11 were evaluated by Western blot. The effect of PPP2R2B on JAK2-STAT3 signaling was studied. Finally, the tumor xenograft model in nude mice was constructed to study the PPP2R2B overexpression on tumor growth in vivo. PPP2R2B was down-regulated in the breast cancer tissues and predicted poor prognosis. PPP2R2B inhibited cell proliferation and induced cell apoptosis. PPP2R2B suppressed cell migration and invasion of MCF-7 and MDA-MB-231 cells. PPP2R2B promoted erastin-induced ferroptosis in breast cancer cells and regulated the expression of GPX4, ACSL4, and SLC7A11. In addition, PPP2R2B inhibited the phosphorylation of JAK2 and STAT3. PPP2R2B also inhibited tumor growth in vivo. PPP2R2B targets the JAK2-STAT3 signaling pathway to regulate cell proliferation, apoptosis, migration, invasion, and ferroptosis in breast cancer cells.