Objective: To explore the effect of circular RNA-0003420 (circ_0003420) in acute myeloid leukemia (AML) relapse and leukemia stem cells (LSCs) properties.
Materials and methods: TRIzol reagent was used to extract total RNA from AML tissues or cells. Cell viability was assessed by Cell Counting Kit-8 and EdU staining assays. Cell apoptosis was determined by flow cytometry.
Results: Compared with normal hematopoietic stem cells, circular RNA hsa-circ_0003420 expression was considerably decreased in non-m3 AML stem cells. Furthermore, the lack of hsa-circ_0003420 is correlated with poor clinical results and impaired therapeutic effects in AML. Overexpression of hsa-circ_0003420 via transfection caused LSC death and inhibited the characteristics of leukemia tumor stem cells, including expression of Homeobox B4 (HOXB4), MYB, and aldehyde dehydrogenase 1 family member A1 (ALDH1A1) axis. Furthermore, hsa-circ_0003420 targets the mRNA of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and hsa-circ_0003420 expression markedly repressed IGF2BP1 levels in LSCs. Restoration of IGF2BP1 eliminated the effect of hsa-circ_0003420 on the replication, apoptosis, and LSC phenotype of KG-1a cells.
Discussion and conclusions: Up-regulation of hsa-circ_0003420 expression in LSCs caused redox disorder, inflammation and apoptosis, suggesting that this protein could be used as a target for the treatment AML.
Keywords: Acute myeloid leukemia; IGF2BP1, apoptosis; KG-1a; hsa-circ_0003420; leukemia stem cell.