miR-137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in melanoma

Ferroptosis is a regulated form of cell death driven by small molecules or conditions that induce lipid-based reactive oxygen species (ROS) accumulation. This form of iron-dependent cell death is morphologically and genetically distinct from apoptosis, necroptosis, and autophagy. miRNAs are known to...

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Published inCell death and differentiation Vol. 25; no. 8; pp. 1457 - 1472
Main Authors Luo, Meiying, Wu, Longfei, Zhang, Kexin, Wang, Hong, Zhang, Tian, Gutierrez, Lucas, O’Connell, Douglas, Zhang, Peng, Li, Yu, Gao, Tongtong, Ren, Wenyan, Yang, Yongfei
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.08.2018
Nature Publishing Group
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Antitumor activity
Apoptosis
Autophagy
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Cycle Analysis
Cell death
Ectopic expression
Ferroptosis
Glutamine
Life Sciences
Malondialdehyde
Melanoma
miRNA
Necroptosis
Phagocytosis
Reactive oxygen species
Stem Cells
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Summary:Ferroptosis is a regulated form of cell death driven by small molecules or conditions that induce lipid-based reactive oxygen species (ROS) accumulation. This form of iron-dependent cell death is morphologically and genetically distinct from apoptosis, necroptosis, and autophagy. miRNAs are known to play crucial roles in diverse fundamental biological processes. However, to date no study has reported miRNA-mediated regulation of ferroptosis. Here we show that miR-137 negatively regulates ferroptosis by directly targeting glutamine transporter SLC1A5 in melanoma cells. Ectopic expression of miR-137 suppressed SLC1A5, resulting in decreased glutamine uptake and malondialdehyde (MDA) accumulation. Meanwhile, antagomir-mediated inactivation of endogenous miR-137 increased the sensitivity of melanoma cells to erastin- and RSL3-induced ferroptosis. Importantly, knockdown of miR-137 increased the antitumor activity of erastin by enhancing ferroptosis both in vitro and in vivo. Collectively, these data indicate that miR-137 plays a novel and indispensable role in ferroptosis by inhibiting glutaminolysis and suggest a potential therapeutic approach for melanoma.
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ISSN:1350-9047
1476-5403
DOI:10.1038/s41418-017-0053-8