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circAFF2 promotes the development of AML by binding to PML mRNA

Oncogene volume 44, pages 1234–1244 (2025)Cite this article

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Abstract

AML is a complex disease caused by multiple molecular mechanisms. As an important regulatory molecule, the role of circRNA in AML is not fully understood. By performing high-throughput sequencing on clinical samples, we systematically identified the differences in circRNA expression and distribution between AML and healthy donor samples. One circular RNA, circAFF2, was found to be significantly upregulated in AML patients. Functional studies showed that knockdown of circAFF2 could significantly inhibit the proliferation of AML cells and promote their apoptosis. Overexpression of circAFF2 can have opposite effects. In vivo experiments showed that transplantation of AML cells with circAFF2 knockdown slowed the proliferation and infiltration and prolonged the survival time of mice compared to controls. Further studies showed that circAFF2 can promote the degradation of PML mRNA by binding to the 3’UTR of PML mRNA, thereby affecting the proliferation and apoptosis of AML cells. In conclusion, our work demonstrates that circAFF2 can bind to PML mRNA to regulate AML cell function, providing new insights into the mechanism of AML development and potential targets for clinical diagnosis and treatment.

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Fig. 1: Identification and verification of circAFF2.
Fig. 2: Knockdown of circAFF2 inhibits the proliferation and promotes apoptosis of AML cells.
Fig. 3: Knockdown of circAFF2 can inhibit the proliferation of AML cells in mice.
Fig. 4: PML was significantly increased by knockdown of circAFF2 in AML cells.
Fig. 5: circAFF2 exerts functions by regulating PML expression.
Fig. 6: circAFF2 promotes the degradation of PML mRNA by binding to its 3′UTR.

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Data availability

All raw data can be accessed in the NCBI GEO database (GSE229582).

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Funding

This research was funded by the National Natural Science Foundation of China (82170170, 81870129, and 82173314) and the Fundamental Research Funds for the Central Universities (2662022SYYJ001).

Author information

Author notes

  1. These authors contributed equally: Lei Yao, Xinyang Zhang, Xiaoqing Li, Jin Xu.

Authors and Affiliations

  1. College of Biomedicine and Health, Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China

    Lei Yao, Fengyue Li, Yuxin Shan, Linli Ren, Chenjian Zhuo, Sisi Liang, Weinan Yin, Mingqian Feng & Chunjiang He

  2. TaiKang Medical School, Wuhan University, Wuhan, China

    Xinyang Zhang, Siqi Yang, Wenbo Chen, Shuliang Chen & Chunjiang He

  3. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Xiaoqing Li & Lingbo Liu

  4. Medical Research Institute, Wuhan University, Wuhan, China

    Jin Xu & Hudan Liu

  5. Hospital of Huazhong Agricultural University, Wuhan, China

    Lu Chen

  6. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Ke Chen

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Contributions

CH, SC, and KC conceived, designed, and supervised the project. HL, LL, and MF provided technical assistance. LY, XZ, XL, JX, SY, FL, YS, LR, LC, and WY collected samples and performed experiments. WC, CZ, and SL performed the bioinformatics analysis. CH, LY, SC, and KC drafted the manuscript with contributions from all authors.

Corresponding authors

Correspondence to Ke Chen, Shuliang Chen or Chunjiang He.

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The authors declare no competing interests.

Ethical approval and informed consent

The study was approved by the Ethics Committee (Institutional Review Board) of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Approved No. of ethics committee: Lingbo Liu 2023#0508). All patients provided written informed consent for participation according to the Declaration of Helsinki and written informed consent for publication. Clinical information was obtained from the medical records. The animal experiments in this study were approved by the Animal Experimental Ethical Committee of the Huazhong Agricultural University. All in vivo operations were performed in accordance with the Guidelines for Animal Experimentation of Huazhong Agricultural University and the National Institute of Health Guide for the Care and Use of Laboratory Animals.

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Yao, L., Zhang, X., Li, X. et al. circAFF2 promotes the development of AML by binding to PML mRNA. Oncogene 44, 1234–1244 (2025). https://doi.org/10.1038/s41388-025-03299-y

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