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MARCH1, transcriptionally regulated by POU2F2, facilitates acute myeloid leukemia progression via inducing MYCT1 degradation

Oncogene volume 44, pages 2983–2996 (2025)Cite this article

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Abstract

Acute myeloid leukemia (AML) is a heterogeneous clonal disease. Membrane-associated ring-CH type finger 1 (MARCH1), a membrane-anchored E3 ubiquitin ligase, is highly expressed in AML. However, its role in AML remains unclear. Our study showed that MARCH1 expression was strongly associated with FAB classifications and the survival of patients with AML. Gain-of-function and loss-of-function experiments showed that MARCH1 promoted the proliferation of AML cells and inhibited apoptosis and differentiation. In vivo, MARCH1 knockdown inhibited the infiltration of AML cells, resulting in prolonged survival of AML mice. In order to illustrate what cause the high expression of MARCH1, we analyzed the promoter region of MARCH1 and found that POU2F2, a transcription factor with high levels in AML, positively regulated the transcription of MARCH1. Finally, we demonstrated that MARCH1 interacted with MYCT1, a candidate tumor suppressor, and accelerated its ubiquitination and degradation. Remarkably, MYCT1 knockdown abolished the inhibitory effects of MARCH1 knockdown on AML cell growth. Our findings indicate that MARCH1, whose transcription is positively modulated by POU2F2, facilitates the malignant behaviors of AML cells through interacting with MYCT1 and accelerating its ubiquitination and degradation. The results implied that targeting MARCH1 might be a promising therapeutic strategy for AML.

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Fig. 1: MARCH1 was elevated in patients with AML.
Fig. 2: MARCH1 promoted proliferation and cell cycle progression of AML cells.
Fig. 3: MARCH1 knockdown enhanced apoptosis and differentiation of AML cells.
Fig. 4: MARCH1 knockdown promoted survival of NOD/SCID mice.
Fig. 5: POU2F2 activated MARCH1 transcription.
Fig. 6: MARCH1 interacted with MYCT1 and promoted its ubiquitination.
Fig. 7: MARCH1 promoted AML progression partially by antagonizing the tumor suppressor effects of MYCT1.
Fig. 8: A scheme of the POU2F2/MARCH1/MYCT1 axis role in AML.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

We thank the staff of Department of Hematology Laboratory of Shengjing Hospital of China Medical University for their suggestions on data collation.

Funding

This work was supported by the National Natural Science Foundation of China (NSFC) [grant number: 82070165], Natural Science Foundation of Liaoning Province [grant number: 2023-MSLH-387], Talent Project of Shengjing Hospital [grant number: M1425 and M0957] and National Natural Science Foundation of China (NSFC) [grant number: 82200227].

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  1. These authors contributed equally: Jianing Liu, Jianan Xu.

Authors and Affiliations

  1. Department of Hematology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China

    Jianing Liu, Rongcan Sun, Xiaohui Wang, Fang Chen, Yu Fu, Henan Zhang, Jihong Zhang & Shuang Fu

  2. Department of Medical Genetics, China Medical University, Shenyang, Liaoning, PR China

    Jianan Xu

  3. Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China

    Bin Wu & Ying Yang

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Contributions

JNL, JNX and SF contributed to the study conception and design. Material preparation, data collection and analysis were performed by JNL, JNX, RCS, XHW, FC, YF, HNZ, BW and YY. The first draft of the manuscript was written by JNL and JNX. Experimental materials and technical support were provided by JHZ. The first draft of the manuscript was reviewed and edited by SF. All authors read and approved the final manuscript.

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Correspondence to Jihong Zhang or Shuang Fu.

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This study was approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. All animal experiments were conducted with the approval by Medical Ethics Committee of Shengjing Hospital of China Medical University, and all procedures were line with the Guide for the Care and Use of Laboratory Animals.

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Liu, J., Xu, J., Sun, R. et al. MARCH1, transcriptionally regulated by POU2F2, facilitates acute myeloid leukemia progression via inducing MYCT1 degradation. Oncogene 44, 2983–2996 (2025). https://doi.org/10.1038/s41388-025-03464-3

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