WANG Yunhui,ZHANG Xiaofeng.. miR-152-3p via AKT/GSK-3β/Nrf2 signaling pathway promoting neuronal ferroptosis in rats with cerebral hemorrhage[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2024, 54(4): 287-295，301.
Abstract：Objective: To explore how miR-152-3p influences neuronal ferroptosis in rats with intracerebral hemorrhage (ICH) through the Akt /GSK-3β/Nrf2 signaling pathway. Methods: Rat neuronal cells were used to create an in vitro ICH model, induced by oxygenated hemoglobin (oxyHb) stimulation. These cells were treated with either a miR-152-3p inhibitor, a PIK3CA inhibitor, or both. Cell apoptosis was assessed using flow cytometry. The expression level of relevant genes and proteins was measured through RT-qPCR and Western blot. Nrf2 protein nuclear translocation was examined via cellular immunofluorescence. Additionally, a dual-luciferase reporter assay was conducted to investigate the interaction between miR-152-3p and PIK3CA. Results: In the ICH cell model, transfection with the miR-152-3p inhibitor significantly reduced apoptosis rate (P<0.01). This treatment also notably increased the expression levels of SLC7A11, GPx4, PIK3CA, and Nrf2 proteins, as well as the p-AKT/AKT ratio, while decreasing GSK-3β protein levels (P<0.01). Furthermore, Nrf2 protein nuclear translocation was significantly enhanced (P<0.01). However, these effects were mitigated upon PIK3CA inhibitor treatment. The luciferase reporter assay confirmed that miR-152-3p could target and regulate PIK3CA. Conclusion: miR-152-3p, through the Akt/GSK-3β/Nrf2 signaling pathway, promotes neuronal ferroptosis in rats experiencing intracerebral hemorrhage.
