miR-126 promotes the growth and proliferation of leukemia stem cells by targeting DNA methyltransferase 1.

Previous studies have showed that the interaction between microRNAs (miRNAs) and leukemia stem cells (LSCs) may be a cause of drug resistance of acute myeloid leukemia (AML). However, whether miR-126 participates in the pathogenesis of AML remains unclear. In our study, we first examined the expression of miR-126 in CD34+ or CD34- cells isolated from blood samples and LSC cell line: KG-1a-LSCs and MOLM13-LSCs by qRT-PCR analysis. Then miR-126 inhibitor and mimics were applied to evaluate the roles of miR-126 in cell proliferation of LSC cell lines using CCK-8 assay and Ki-67 staining. Moreover, flow cytometry analysis was used to assess the apoptosis of LSC cell lines treated with miR-126 inhibitor of mimics. In addition, we analyzed the relationship between miR-126 and DNA methyltransferase 1 (DNMT1) by bioinformatics analysis and dual-luciferase reporter assay. Western blot analysis was applied to examine the protein expression level of DNMT1 in miR-126 mimics treated LSC cells. Results showed that miR-126 expression was significantly higher in CD34+ cells and KG-1a-LSCs and MOLM13-LSCs. Knockdown of miR-126 in KG-1a-LSCs and MOLM13-LSCs inhibited cell proliferation, and promoted apoptosis. miR-126 could regulate DNA methyltransferase 1 (DNMT1) expression by directly binding to it. In conclusion, these findings suggested that miR-126 may promote cell proliferation of LSCs by targeting DNMT1.