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A novel Twist1/hsa-miR138-5p/caspase-3 pathway regulates cell proliferation and apoptosis of human multiple myeloma

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Abstract

The nuclear transcription factor twist-related protein 1 (Twist1) is associated with tumor malignant transformation and metastasis in various types of carcinomas. We found that Twist1 was highly expressed in clinical multiple myeloma (MM) cells, and explored its roles in proliferation and apoptosis in human MM cell lines U266 and RPMI-8226. In these cells, Twist1 transcriptionally regulated the miRNA hsa-miR138-5p, which targeted caspase-3 to control apoptosis. Silencing of Twist1 significantly suppressed cell proliferation and increased apoptosis, which was reversed by overexpression of hsa-miR138-5p or simultaneous silencing of caspase-3. This reversion was further substantiated by attenuated apoptotic signaling, including downregulated expression of the cleaved forms of caspase-3 and peroxisome proliferator-activated receptor 1 (PPAR1). We demonstrate here for the first time that the novel Twist1/hsa-miR138-5p/caspase-3 pathway contributes significantly to the proliferation and survival of human MM cells. Our study provides new insight for novel MM treatments by developing Twist1-targeted therapeutics.

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Author notes

  1. Wenjiao Qin and Qin Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China

    Wenjiao Qin & Xiaoping Xu

  2. Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China

    Qin Liu, Aiping Liu, Huating Zhang & Tao Zhang

  3. Worldwide Medical Center, Huashan Hospital, Fudan University, Shanghai, China

    Jingwen Gu

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  1. Wenjiao Qin
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  2. Qin Liu
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  3. Xiaoping Xu
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  4. Aiping Liu
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  5. Huating Zhang
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  6. Jingwen Gu
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  7. Tao Zhang
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Correspondence to Jingwen Gu or Tao Zhang.

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This study was approved by the Ethics Review Committee at the Huashan Hospital of Fudan University. Written, informed consent was obtained from all participants in accordance with the ethical committee standards.

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The authors declare that they have no conflict of interest.

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Qin, W., Liu, Q., Xu, X. et al. A novel Twist1/hsa-miR138-5p/caspase-3 pathway regulates cell proliferation and apoptosis of human multiple myeloma. Ann Hematol 100, 1815–1824 (2021). https://doi.org/10.1007/s00277-020-04059-6

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  • DOI: https://doi.org/10.1007/s00277-020-04059-6

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