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Multiple myeloma with high expression of SLC7A11 is sensitive to erastin-induced ferroptosis

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Abstract

Ferroptosis, a nonapoptotic form of cell death marked by iron-dependent peroxidation of phospholipids, is associated with the occurrence and progression of tumors. Erastin, a selective inhibitor of the cystine/glutamate transporter system Xc−, can induce the ferroptosis of cancer cells. Multiple myeloma (MM) has been reported to be insensitive to erastin-induced ferroptosis. However, we found the erastin sensitivity of different MM cells varied widely. Specifically, SLC7A11 abundance determined the sensitivity of MM cells to erastin-induced ferroptosis. MM cells expressing a high SLC7A11 level were more sensitive to erastin-induced ferroptosis than cells expressing a low level of SLC7A11. Moreover, the expression of SLC7A11 gradually increased with the progression of plasma cell dyscrasias. Survival analysis indicated that high levels of SLC7A11 predicted a poor prognosis for MM patients. Knocking down SLC7A11 expression significantly inhibited the proliferation of MM cells and induced ferroptotic cell death. Additionally, we revealed that the long noncoding RNA (lncRNA) SLC7A11-AS1 was a critical regulatory factor of SLC7A11 expression. SLC7A11-AS1 overexpression diminished SLC7A11 levels, leading to the ferroptosis of MM cells. In summary, our data show that heterogeneous SLC7A11 expression affects MM cell sensitivity to ferroptosis, providing a theoretical basis for improving the clinical treatment of MM.

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Data availability

The data supporting the findings of this study can be found in the article, Supplementary Information, or available from the corresponding author upon reasonable request.

Abbreviations

MM:

Multiple myeloma

GSH:

Glutathione

ROS:

Reactive oxygen species

SLC7A11:

Subunit solute carrier family 7 member 11

GPX4:

Glutathione peroxidase 4

OS:

Overall survival

PFS:

Progression-free survival

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Funding

The research leading to these results has received funding from Natural Science Foundation of China (82270197, 82270211), The special project of “Technological innovation” project of CNNC Medical Industry Co. Ltd (ZHYLYB2021002), Natural Science Foundation of Jiangsu Province China (BK20201408).

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Author notes

  1. Weimin Zhang and Qi Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, The Second Affiliated Hospital of Soochow University, San Xiang Road 1055, Suzhou, 215006, China

    Weimin Zhang, Qi Li, Yuchen Zhang, Shushu Yuan, Xinyun Zhang, Meifang Zhao & Bingzong Li

  2. Department of Cell Biology, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Ren Ai Road 199, Suzhou, 215123, China

    Zhiming Wang & Wenzhuo Zhuang

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  1. Weimin Zhang
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Contributions

BL and WZ designed the research, and contributed reagents and other essential materials. WZ performed research, QL wrote the paper, YZ, ZW, SY, XZ, MZ modified the paper.

Corresponding authors

Correspondence to Wenzhuo Zhuang or Bingzong Li.

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The authors declare that they have no competing interests.

Ethical approval

The animal experimentation acquired permission from the ethics committee of Soochow university. All MM patient samples were collected from the Second Affiliated Hospital of Soochow University after receiving permission from the ethics committee of the second affiliated hospital of Soochow university. Informed written consent was obtained from each subject or each subject's guardian. The study was conducted in accordance with the Declaration of Helsinki.

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Zhang, W., Li, Q., Zhang, Y. et al. Multiple myeloma with high expression of SLC7A11 is sensitive to erastin-induced ferroptosis. Apoptosis 29, 412–423 (2024). https://doi.org/10.1007/s10495-023-01909-2

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