MicroRNA‐9 plays a role in interleukin‐10‐mediated expression of E‐cadherin in acute myelogenous leukemia cells

We previously showed that the CD82/signal transducer and activator of transcription/interleukin‐10 (IL‐10) axis is activated in CD34+/CD38− AML cells that favor the bone marrow microenvironment. The present study explored the novel biological function of IL‐10 in regulation of expression of adhesion molecules in AML cells and found that exposing AML cells to IL‐10 induced expression of E‐cadherin, but not other adhesion molecules, including VLA4, CD29, and LFA1. Downregulation of E‐cadherin with an siRNA suppressed the adhesion of leukemia cells to bone marrow‐derived mesenchymal stem cells and enhanced the anti‐leukemia effect of cytarabine. A microRNA (miRNA) database search identified an miR‐9 as a candidate miRNA binding onto the 3′‐UTR of E‐cadherin and regulating its expression. Notably, treatment of leukemia cells with IL‐10 decreased miR‐9 expression through hypermethylation of the miR‐9 CpG islands. In addition, downregulation of DNA methyltransferase 3A by siRNAs decreased E‐cadherin expression in parallel with an increase in levels of miR‐9 in leukemia cells. Notably, short hairpin RNA‐mediated IL‐10 downregulation impaired engraftment of human AML cells and enhanced the anti‐leukemia effect of cytarabine in conjunction with miR‐9 upregulation and E‐cadherin downregulation in a human AML xenograft model. Taken together, the IL‐10/E‐cadherin axis may be a promising therapeutic target for treating AML. The present study explored the novel biological function of IL‐10 in regulation of expression of adhesion molecules in AML cells and found that exposing AML cells to IL‐10 induced expression of E‐cadherin. IL‐10/E‐cadherin axis may be a promising therapeutic target for treating AML.