TUG1 confers Adriamycin resistance in acute myeloid leukemia by epigenetically suppressing miR-34a expression via EZH2

Increasing evidence has suggested the involvement of long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in acute myeloid leukemia (AML) chemoresistance are still not well elucidated. In the present study, we investigate the functional role of TUG1 in Adriamycin (ADR) resistance of AML and discover the underlying molecular mechanism. Our study revealed that TUG1 was up-regulated in ADR-resistant AML tissues and cells. High TUG1 expression was correlated with poor prognosis of AML patients. TUG1 knockdown improved the sensitivity of HL60/ADR cells to ADR. Moreover, TUG1 could epigenetically suppress miR-34a expression via recruiting Enhancer of zeste homolog 2 (EZH2). miR-34a overexpression could mimic the functional role of down-regulated TUG1 in ADR resistance. miR-34a knockdown counteracted the inductive effect of TUG1 inhibition on ADR sensitivity of HL60/ADR cells. Furthermore, TUG1 knockdown facilitated ADR sensitivity of ADR-resistant AML cells in vivo. In summary, TUG1 knockdown overcame ADR resistance of AML by epigenetically enhancing miR-34a expression, providing a novel therapeutic target for AML.