lncRNA MEG3 promotes hypoxia/reoxygenation-induced ferroptosis and cell injury in H9C2 cells through regulating the miR-22/TP53 axis

Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is crucial in cerebral ischemia/reperfusion and cardiovascular cell injury. However, the effect of lncRNA MEG3 on ferroptosis due to myocardial ischemia/reperfusion is unknown. Hypoxia/reoxygenation (H/R) H9C2 cell model was constructed. qRT-PCR detected MEG3, miR-22 and tumor protein 53 (TP53) expression, and the location of MEG3 was assessed by RNA FISH. Dual luciferase assay was employed to verify whether lncRNA MEG3 targets and regulates miR-22. Cell counting kit-8 assay and EdU staining assessed cell proliferation, and flow cytometry assessed apoptosis rate. The FerroOrange fluorescent probe and Fe2+ assay kit were used to detect Fe2+ levels, and different kits to determine oxidative stress and inflammatory factors levels. Ferroptosis-related proteins levels were assessed via Western blot. H9C2 cell viability and proliferation were reduced, while apoptosis and pro-inflammatory factors were elevated after H/R. lncRNA MEG3 was upregulated in H/R-treated H9C2 cells, overexpression MEG3 increased Fe2+ and oxidative stress levels, up-regulated ferroptosis-related proteins, and knockdown MEG3 reversed the above metrics. Additionally, MEG3 regulated miR-22/TP53 axis, silencing miR-22 promoted H9C2 cell injury and ferroptosis, whereas overexpression miR-22 increased the protective impact of knockdown MEG3 on H9C2 cells. lncRNA MEG3 promotes ferroptosis caused by H/R by modulating miR-22/TP53 in H9C2 cells.