Long noncoding RNA MEG3 inhibits proliferation of chronic myeloid leukemia cells by sponging microRNA21

[Display omitted] •LncRNA MEG3 was downregulated and miR-21 was upregulated in advanced-stage CML.•MEG3 overexpression and knockdown of miR-21 inhibited proliferation and promoted apoptosis.•LncRNA MEG3 and miR21 may serve as novel therapeutic targets for CML blast crisis; demethylation drugs might also have potential clinical applications. The long noncoding RNA (lnc) maternally expressed 3 (MEG3) is downregulated in many types of cancers. However, the relationship between lncRNA MEG3, microRNA-21 (miR-21) and chronic myeloid leukemia (CML) blast crisis is unknown. This study examined bone marrow samples from 40 CML patients and 10 healthy donors. Proliferation and apoptosis assays, real-time polymerase chain reaction (PCR), bisulfite sequencing PCR, Western blotting, luciferase assay, RNA pull-down, RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP) and Chromatin immunoprecipitation (ChIP) were performed. We found that MEG3 and PTEN expression were down-regulated, whereas, MDM2, DNMT1 and miR-21 were up-regulated in the accelerated and blast phases of CML. Treated with 5-azacytidine decreased the level of MDM2, DNMT1 and miR21, but increased the level of MEG3 and PTEN. Overexpression of MEG3 and silencing the expression of miR-21 inhibited proliferation and induced apoptosis. MEG3 overexpression and silencing the expression of miR21 influence the levels of MMP-2, MMP-9, bcl-2 and Bax. MEG3 was able to interact with MDM2 and EZH2. MDM2 could interact with DNMT1 and PTEN. MYC and AKT can interact with EZH2. ChIP-seq showed that the promoter of KLF4 and SFRP2 interacts with DNMT1. In conclusion, lncRNA MEG3 and its target miR21 may serve as novel therapeutic targets for CML blast crisis; and demethylation drugs might also have potential clinical application in treating CML blast crisis.