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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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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We would like to acknowledge our lab colleagues for the support in the work of this study.
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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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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.
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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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DOI: https://doi.org/10.1007/s10565-023-09792-y