MiR‐9 regulates ferroptosis by targeting glutamic‐oxaloacetic transaminase GOT1 in melanoma. Issue 11 (14th August 2018)

• Record Type: Journal Article
• Authors: Zhang, Kexin; Wu, Longfei; Zhang, Peng; Luo, Meiying; Du, Jing; Gao, Tongtong; O'Connell, Douglas; Wang, Gaoyang; Wang, Hong; Yang, Yongfei
• Is Part Of: Molecular carcinogenesis. Volume 57:Issue 11(2018)
• Page Start: 1566
• Page End: 1576
• Publication Date: 2018-08-14
• Subjects: ferroptosis -- GOT1 -- glutaminolysis -- melanoma -- miR‐9; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22878
• Languages: English
• ISSNs: 0899-1987

Abstract

Abstract : 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.