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

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 of AML 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 (CRISPR CAS9) 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.