LncRNA NEAT1 restrains the malignant biological characteristics of acute myeloid leukemia via regulating CTCF/CXCR2 axis

Sep 30, 2026

Acute myeloid leukemia (AML) is marked by poor treatment efficacy, frustrating prognosis, and frequent refractory or relapsed disease. This study reports atypically low NEAT1 expression in clinical AML specimens and AML cell lines, while NEAT1 overexpression suppresses malignant proliferation and colony formation and promotes apoptosis. RNA pull down, RIP, and ChIP showed NEAT1 interacts with CTCF, linking CTCF to CXCR2 regulation. NEAT1 further down-regulates MYC to activate the CTCF/CXCR2 axis; CTCF or CXCR2 inhibition and knockout reverse NEAT1-driven AML progression, supported by in vivo data.

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Clinical and Experimental Medicine (2026) 26:93 [https://doi.org/10.1007/s10238-025-01975-7](https://doi.org/10.1007/s10238-025-01975-7) RESEARCH LncRNA NEAT1 restrains the malignant biological characteristics of acute myeloid leukemia via regulating CTCF/CXCR2 axis Yanquan Liu1 · Zuotao Li2 · Jingdong Zhang1 · Jianzhen Shen3 · Hehui Zhang2 · Yue Yin3 · Lei Sun4 · HuanwenTang4 Received: 11 August 2025 / Accepted: 8 November 2025 © The Author(s) 2025 Abstract Acute myeloid leukemia (AML) is notorious in the field of hematology for its poor efficacy, frustrating prognosis, and it is prone to refractory or relapsed conditions. Previous studies in our team have shown that some Long noncoding RNAs (lncRNAs) and chemokine receptors play key regulatory roles in AML. The findings of this study demonstrated that the expression of NEAT1 was atypically low in both clinical AML specimens and AML cell lines. Overexpression of NEAT1 was capable of attenuating the malignant biological characteristics ofAML cells, including inhibiting the malignant proliferation and colony formation of leukemia cells, and facilitating cell apoptosis. We identified and clarified the binding capacity or interaction between NEAT1 and CTCF as well as CTCF and CXCR by employing experimental techniques such as RNA pull down, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) . Additionally, our previous studies have affirmed that CXCR2 plays an indispensable role in the pathogenesis of leukemia, and what is astonishing in this study is that CTCF might have a targeted regulatory relationship with CXCR2 . CTCF was identified as a NEAT1 target and transcriptionally activated the expression of CXCR2 in AML cells. Correspondingly, we also discovered that NEAT1 could influence the malignant biological behavior of AML cells by down-regulating MYC to activate the CTCF/CXCR2 signaling axis. In salvage experiments, targeted inhibition of CTCF and CXCR2 knockout (CRISPRCAS9) reversed the promoting effect of NEAT1 inactivation on AML progression and suppressed the malignant phenotype. More importantly, the in vivo experiments in this study corroborate the reliability of the conclusions drawn from in vitro cell experiments and further demonstrate that LncRNA NEAT1 inhibits the malignant biological characteristics of acute myeloid leukemia by mediating the CTCF/CXCR2 regulatory axis. Keywords Leukemic cell · Cell therapy · Acute myeloid leukemia · Gene therapy · LncRNA NEAT1 · CTCF/CXCR2 axis · Molecular mechanism · Targeted therapy Yanquan Liu and Zuotao Li contributed equally to this work. 􀀍 Yanquan Liu [doctorliuyanquan@gdmu.edu.cn](doctorliuyanquan@gdmu.edu.cn) 1 Jiangxi Health Commission Key Laboratory of Leukemia, Jiangxi Medical College, The Affiliated Ganzhou Hospital (Ganzhou People’s Hospital), Nanchang University, Ganzhou 341000, China 2 The First Affiliated Hospital (the First Clinical Medical College) of Gannan Medical University, Ganzhou 341000, China 3 Fujian Institute of Hematology, National Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, China 4 Department of Hematology, Dongguan Key Laboratory of Environmental Medicine, School of Public Health, The First Dongguan Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Dongguan 523808, Guangdong, China 1 3 Introduction Acute myeloid leukemia (AML), the most common nonsolid hematological malignancy in adults, has adverse biological characteristics such as high heterogeneity, high malignancy and high invasion and metastasis [1, 2] . Despite continuous innovation and progress in the treatment of AML, the prognosis of patients withAML is not optimistic, and AML is still the leading cause of hematological malignancy related death worldwide [3, 4] . As a malignant proliferative disease group of myeloid primordial cells, AMLis characterized by rapid onset, systemic spread and insensitivity to chemoth

FAQs

How does NEAT1 expression relate to AML in this study?

NEAT1 expression is atypically low in both clinical AML specimens and AML cell lines. Increasing NEAT1 attenuates AML malignant behaviors.

What molecular interactions connect NEAT1 to CTCF and CXCR2?

Experimental assays indicate NEAT1 can bind/interact with CTCF, and CTCF transcriptionally activates CXCR2 in AML cells.

What happens when CTCF or CXCR2 is inhibited or knocked out?

Targeted inhibition of CTCF and CXCR2 knockout reverse the pro-progression effects of NEAT1 inactivation on AML progression and suppress malignant phenotypes.

Sep 30, 2026

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