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Updated: Feb 15, 2026
Glutamine Flux Imaging Using Genetically Encoded Sensors
Published on: July 31, 2014
miR-137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in melanoma
Meiying Luo1, Longfei Wu2, Kexin Zhang1
1School of Life Science, Beijing Institute of Technology, Beijing, 100081, China.
Abstract:
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.
Insights
MicroRNA-137 (miR-137) inhibits ferroptosis, a form of cell death, by targeting the glutamine transporter SLC1A5 in melanoma. This finding suggests miR-137 as a potential therapeutic target for melanoma treatment.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- Ferroptosis is a distinct, iron-dependent cell death pathway involving lipid-reactive oxygen species (ROS).
- MicroRNAs (miRNAs) regulate fundamental biological processes, but their role in ferroptosis remains unexplored.
- Melanoma cell death pathways are critical targets for cancer therapy.
Purpose of the Study:
- To investigate the role of miRNA-mediated regulation in ferroptosis.
- To identify specific miRNAs and their targets involved in ferroptosis in melanoma cells.
- To explore the therapeutic potential of targeting miRNA-regulated ferroptosis in melanoma.
Main Methods:
- Investigated miR-137's function in regulating ferroptosis in melanoma cells.
- Utilized ectopic expression and antagomir-mediated inactivation of miR-137.
- Assessed SLC1A5 expression, glutamine uptake, and malondialdehyde (MDA) accumulation.
- Evaluated erastin and RSL3 sensitivity and antitumor activity in vitro and in vivo.
Main Results:
- miR-137 directly targets and suppresses the glutamine transporter SLC1A5 in melanoma.
- Ectopic miR-137 expression reduced glutamine uptake and MDA accumulation, inhibiting ferroptosis.
- Inactivation of miR-137 increased melanoma cell sensitivity to ferroptosis inducers.
- miR-137 knockdown enhanced erastin's antitumor effects by promoting ferroptosis.
Conclusions:
- miR-137 negatively regulates ferroptosis by targeting SLC1A5 and inhibiting glutaminolysis.
- miR-137 plays a critical role in controlling ferroptosis in melanoma.
- Targeting miR-137 presents a potential therapeutic strategy for melanoma.
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