Epigenetic silencing of E‐cadherin gene induced by lncRNA MALAT‐1 in acute myeloid leukaemia

BACKGROUND: Epigenetic abnormalities in acute myeloid leukaemia provide us with a target for novel therapeutic strategies. The aim of the study was to verify the epigenetic regulatory mechanism of E‐cadherin gene silencing induced by long non‐coding RNA MALAT‐1 in AML. METHODS: Expression of MALAT‐1, E‐cadherin, EZH2, SUZ12 and EED genes in AML patients was detected by RT‐qPCR. After MALAT‐1 silencing in AML cell lines, levels of the E‐cadherin, EZH2, SUZ12, EED, DNMT1, DNMT3A and DNMT3B genes and encoded proteins were detected by RT‐qPCR and Western blotting. The level of CpG island methylation and trimethylation modification of histone H3K27 in the promoter region of E‐cadherin was detected by pyrosequencing and ChIP‐qPCR. RIP‐qPCR was used to detect the interaction between MALAT‐1 and proteins. RESULTS: MALAT‐1, EZH2 and EED gene expression was markedly increased in AML patients with E‐cadherin down‐regulation. A positive correlation between EZH2 or SUZ12 and MALAT‐1 expression was observed. After MALAT‐1 silencing, the expression of E‐cadherin was up‐regulated, whereas the expression of EZH2, SUZ12, DNMT1, DNMT3A and DNMT3B was down‐regulated. Results of Western blotting were consistent with those of RT‐qPCR. Methylation levels of E‐cadherin in AML patients were higher than that in normal controls, which appeared to increase with age. Methylation of the CpG island and H3K27 trimethylation of E‐cadherin were decreased after MALAT‐1 silencing. RIP‐qPCR suggested that MALAT‐1 might be enriched by EZH2 and SUZ12. CONCLUSION: Our findings verified that MALAT‐1 might lead to the transcriptional silencing of E‐cadherin gene through the trimethylation of H3K27 mediated by recruiting EZH2 and SUZ12.