Silencing long non-coding RNA HOTAIR exerts anti-oncogenic effect on human acute myeloid leukemia via demethylation of HOXA5 by inhibiting Dnmt3b

Cancer Cell Int. 2019 Apr 29;19:114. doi: 10.1186/s12935-019-0808-z. eCollection 2019.

Abstract

Background: As an aggressive hematological malignancy, acute myeloid leukemia (AML) remains a dismal disease with poor prognosis. Long non-coding RNAs (lncRNAs) have been widely reported to be involved in tumorigenesis of AML. Here, we define an important role of lncRNA HOTAIR in AML in relation to HOXA5 methylation.

Methods: Firstly, the expression of HOTAIR was examined in AML samples and cells collected. Next, gain- or loss-of function experiments were conducted in AML cells to explore the effect of HOTAIR on AML. Then, relationship among HOXA5 promoter methylation, HOTAIR and Dnmt3b was measured. Expression of HOXA5 and cell proliferation/apoptosis-related genes was also detected. A last, in vivo assay was performed to assess the tumor formation in nude mice in order to explore the roles of HOTAIR and HOXA5 in cell apoptosis and proliferation.

Results: LncRNA HOTAIR was found to be upregulated in AML cells and tissues. With silencing of HOTAIR and overexpression of HOXA5, AML cell proliferation was decreased while the apoptosis was induced. Furthermore, HOTAIR was observed to recruit Dnmt3b and to increase HOXA5 promoter methylation. Moreover, silencing HOTAIR and upregulating HOXA5 were found to induce apoptosis and reduce proliferation of AML cells in vivo.

Conclusion: Our findings highlight the anti-tumor ability of HOTAIR silencing in AML, suggesting that silencing HOTAIR was able to inhibit AML progression through HOXA5 promoter demethylation by decreasing Dnmt3b.

Keywords: Acute myeloid leukemia; Apoptosis; Dnmt3b; HOXA5; Long noncoding RNA HOTAIR; Proliferation; Promoter methylation.