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ZFX-mediated upregulation of CEBPA-AS1 contributes to acute myeloid leukemia progression through miR-24-3p/CTBP2 axis

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Abstract

Emerging reports demonstrated that long non-coding RNAs (lncRNAs) play a role in the pathogenesis and metastasis of cancers. However, the biological functions and underlying mechanisms of LncRNA CEBPA-AS1 in acute myeloid leukemia (AML) remain largely elusive. The level of CEBPA-AS1 was examined in AML clinical tissues and cell lines via fluorescence in situ hybridization (FISH) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In vivo and in vitro functional tests were applied to identify the pro-oncogenic role of CEBPA-AS1 in AML development. The overexpressed CEBPA-AS1 was linked to poor survival in AML patients. Moreover, the relationships among CEBPA-AS1, Zinc Finger Protein X-Linked (ZFX), and miR-24-3p were predicted by bioinformatics and validated by RNA immunoprecipitation (RIP) and luciferase reporter assays. Our findings unveiled that transcription factor ZFX particularly interacted with the promoter of CEBPA-AS1 and activated CEBPA-AS1 transcription. Downregulation of CEBPA-AS1 inhibited the proliferation and invasion while promoted apoptosis of AML cells in in vitro, as well as in vivo, xenograft tumor growth was modified. However, overexpression of CEBPA-AS1 observed the opposite effects. Furthermore, CEBPA-AS1 acted as a competitive endogenous RNA (ceRNA) of miR-24-3p to attenuate the repressive effects of miR-24-3p on its downstream target CTBP2. Taken together, this study emphasized the pro-oncogenic role of CEBPA-AS1 in AML and illustrated its connections with the upstream transcription factor ZFX and the downstream regulative axis miR-24-3p/CTBP2, providing important insights to the cancerogenic process in AML.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to acknowledge our lab colleagues for the support in the work of this study.

Funding

This work was financially supported by Special Funds for Education and Scientific Research of Fujian Province Finance Department Units (2019–926) and Subsidy Funds for Medical Double-High Project of Fujian Province.

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Author notes

  1. Chengyi Wang and Chao-Min Song contributed equally to the work.

Authors and Affiliations

  1. Department of Pediatrics, Fujian Branch of Shanghai Children’s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China

    Chengyi Wang, Shan Liu, Lu-Min Chen, Shu-Fang Xue, Si-Han Huang, Han Lin & Guang-Hua Liu

  2. Fujian Children’s Hospital, Fuzhou, China

    Chengyi Wang, Shan Liu, Lu-Min Chen, Shu-Fang Xue, Si-Han Huang, Han Lin & Guang-Hua Liu

  3. Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China

    Chengyi Wang, Shan Liu, Lu-Min Chen, Shu-Fang Xue, Si-Han Huang, Han Lin & Guang-Hua Liu

  4. Department of Neonatology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China

    Chao-Min Song

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Contributions

Conception and design of the research: CYW, CMS, and GHL. Acquisition of data: SFX, SL, and SHH. Analysis and interpretation of data: SL and LMC. Statistical analysis: CYW and CMS. Obtaining funding: CYW and GHL. Drafting the manuscript: CYW, CMS, and GHL. Revision of manuscript for important intellectual content: CYW, CMS, and GHL.

Corresponding author

Correspondence to Guang-Hua Liu.

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This study was approved by the Ethics Committee of Fujian Maternity and Child Health Hospital (No. 2021KLRD636).

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Wang, C., Song, CM., Liu, S. et al. ZFX-mediated upregulation of CEBPA-AS1 contributes to acute myeloid leukemia progression through miR-24-3p/CTBP2 axis. Cell Biol Toxicol 39, 2631–2645 (2023). https://doi.org/10.1007/s10565-023-09792-y

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