Molecular Therapy
Volume 29, Issue 1, 6 January 2021, Pages 263-274
Journal home page for Molecular Therapy

Original Article
A Nuclear Long Non-Coding RNA LINC00618 Accelerates Ferroptosis in a Manner Dependent upon Apoptosis

https://doi.org/10.1016/j.ymthe.2020.09.024Get rights and content
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Ferroptosis is primarily caused by intracellular iron catalytic activity and lipid peroxidation. The potential interplay between ferroptosis and apoptosis remains poorly understood. Here, we show that the expression of a nuclear long non-coding RNA (lncRNA), LINC00618, is reduced in human leukemia and strongly increased by vincristine (VCR) treatment. Furthermore, LINC00618 promotes apoptosis by increasing the levels of BCL2-Associated X (BAX) and cleavage of caspase-3. LINC00618 also accelerates ferroptosis by increasing the levels of lipid reactive oxygen species (ROS) and iron, two surrogate markers of ferroptosis, and decreasing the expression of solute carrier family 7 member 11 (SLC7A11). Interestingly, VCR-induced ferroptosis and apoptosis are promoted by LINC00618, and LINC00618 accelerates ferroptosis in a manner dependent upon apoptosis. LINC00618 attenuates the expression of lymphoid-specific helicase (LSH), and LSH enhances the transcription of SLC7A11 after the recruitment to the promoter regions of SLC7A11, further inhibiting ferroptosis. Knowledge of these mechanisms demonstrates that lncRNAs related to ferroptosis and apoptosis are critical to leukemogenesis and chemotherapy.

Keywords

LINC00618
apoptosis
ferroptosis
vincristine
leukemia
lymphoid-specific helicase
solute carrier family 7 member 11

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These authors contributed equally to this work.