Long noncoding RNA SENCR facilitates the progression of acute myeloid leukemia through the miR-4731-5p/IRF2 pathway.

Abstract

Acute myeloid leukemia (AML) is a type of hematological tumor caused by malignant clone hematopoietic stem cells. The relationship between lncRNAs and tumor occurrence and progression has been gaining attention. Research has shown that Smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) is abnormally expressed in various diseases, whereas its role in AML is still poorly understood. The expression of SENCR, microRNA-4731-5p (miR-4731-5p) and Interferon regulatory factor 2 (IRF2) were measured using qRT-PCR. The proliferation, cycle and apoptosis of AML cells with or without knockdown of SENCR were detected by CCK-8 assay, EdU assay, flow cytometry, western blotting and TUNEL assay, respectively. Consistently, SENCR knockdown was impaired the AML progression in immunodeficient mice. In addition, the binding of miR-4731-5p to SENCR or IRF2 was confirmed by luciferase reporter genes assay. Finally, rescue experiments were conducted to confirm the role of SENCR/miR-4731-5p/IRF2 axis in AML. SENCR is highly expressed in AML patients and cell lines. The patients with high SENCR expression had poorer prognosis compared with those with low SENCR expression. Interestingly, knockdown of SENCR inhibits the growth of AML cells. Further results demonstrated that the reduction of SENCR slows the progression of AML in vivo. SENCR could function as a competing endogenous RNA (ceRNA) to negatively regulate miR-4731-5p in AML cells. Furthermore, IRF2 was validated as a direct target gene of miR-4731-5p in AML cells. Our findings underscore the important role of SENCR in regulating the malignant phenotype of AML cells by targeting the miR-4731-5p/IRF2 axis.