A Nuclear Long Non-Coding RNA LINC00618 Accelerates Ferroptosis in a Manner Dependent upon Apoptosis.
A Nuclear Long Non-Coding RNA LINC00618 Accelerates Ferroptosis in a Manner Dependent upon Apoptosis.
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核长非编码 RNA LINC00618 以依赖于细胞凋亡的方式加速铁死亡
DOI：
10.1016/j.ymthe.2020.09.024
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发表时间：
2021-01-06
期刊：
影响因子：
--
通讯作者：
Tao Y
中科院分区：
文献类型：
--
作者：
Wang Z;Chen X;Liu N;Shi Y;Liu Y;Ouyang L;Tam S;Xiao D;Liu S;Wen F;Tao Y
铁凋亡主要是由细胞内铁催化活性和脂质过氧化引起的。铁凋亡和细胞凋亡之间的潜在相互作用仍然知之甚少。在这里，我们表明，表达的核长非编码RNA（lncRNA），LINC 00618，是减少在人类白血病和强烈增加长春新碱（VCR）治疗。此外，LINC 00618通过增加BCL 2相关X（BAX）的水平和半胱天冬酶-3的裂解来促进细胞凋亡。LINC 00618还通过增加脂质活性氧（ROS）和铁（铁凋亡的两种替代标志物）的水平以及降低溶质载体家族7成员11（SLC 7A 11）的表达来加速铁凋亡。有趣的是，VCR诱导的铁凋亡和细胞凋亡被LINC 00618促进，LINC 00618以依赖于细胞凋亡的方式加速铁凋亡。LINC 00618减弱淋巴特异性解旋酶（LSH）的表达，并且LSH在募集到SLC 7A 11的启动子区域后增强SLC 7A 11的转录，从而进一步抑制铁凋亡。这些机制的知识表明，与铁凋亡和细胞凋亡相关的lncRNA是白血病发生和化疗的关键。我们确定了一个以前未知的功能，特定的lncRNA，LINC 00618，我们表明促进细胞凋亡和铁凋亡的表观遗传机制，从而连接细胞凋亡和铁凋亡。LINC 00618与长春新碱协同作用，有望成为白血病治疗的新靶点。
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. We identified a previously unknown function of a specific lncRNA, LINC00618, which we show promotes apoptosis and ferroptosis by epigenetic mechanisms, thereby linking apoptosis and ferroptosis. In cooperation with vincristine, LINC00618 may represent a promising target for leukemia therapy.
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