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FTO promotes Bortezomib resistance via m6A-dependent destabilization of SOD2 expression in multiple myeloma

Cancer Gene Therapy volume 30, pages 622–628 (2023)Cite this article

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Abstract

Drug resistance is the main reason for the failure of Bortezomib (Bort) in the treatment of multiple myeloma (MM), which seriously affects the efficacy of Bort. Therefore, the exploration of Bort resistance to treat MM will be very beneficial. Thus, this study aims to study the function and mechanism of Fat mass and obesity associated (FTO) on the Bort resistance of MM. In the present study, we demonstrated that FTO promotes Bort resistance via m6A-dependent destabilization of SOD2 expression in MM. These findings may provide a substantial evidence for the Bort resistance in MM.

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Fig. 1: FTO was highly expressed in different MM cell lines.
Fig. 2: FTO promoted MM progression and Bort resistance.
Fig. 3: FTO interacted with SOD2.
Fig. 4: SOD2 was significantly downregulated in JJN3 cell lines and treatment with Bort.
Fig. 5: SOD2 suppressed MM progression and Bort resistance.
Fig. 6: FTO promoted MM progression and Bort resistance in vivo.
Fig. 7: FTO promoted Bort resistance in MM through m6A demethylation of SOD2.

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Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China

    Chong Wang, Lingling Li, Mengya Li, Weiqiong Wang & Zhongxing Jiang

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  1. Chong Wang
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  2. Lingling Li
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CW conceived and designed the experiments, LL & ML analyzed and interpreted the results of the experiments, CW, WW & ZJ performed the experiments.

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Correspondence to Chong Wang.

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Wang, C., Li, L., Li, M. et al. FTO promotes Bortezomib resistance via m6A-dependent destabilization of SOD2 expression in multiple myeloma. Cancer Gene Ther 30, 622–628 (2023). https://doi.org/10.1038/s41417-022-00429-6

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