miR-9 regulates ferroptosis by targeting glutamic-oxaloacetic transaminase GOT1 in melanoma

Ferroptosis is a recently recognized form of regulated cell death driven by lipid-based reactive oxygen species (ROS) accumulation. However, the molecular mechanisms of ferroptosis regulation are still largely unknown. Here we identified a novel miRNA, miR-9, as an important regulator of ferroptosis by directly targeting GOT1 in melanoma cells. Overexpression of miR-9 suppressed GOT1 by directly binding to its 3-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. Conversely, suppression of miR-9 increased the sensitivity of melanoma cells to erastin and RSL3. Importantly, anti-miR-9 mediated lipid ROS accumulation and ferroptotic cell death could be abrogated by inhibiting glutaminolysis process. Taken together, our findings demonstrate that miR-9 regulates ferroptosis by targeting GOT1 in melanoma cells, illustrating the important role of miRNA in ferroptosis.