Long noncoding RNA ZFAS1 enhances adriamycin resistance in pediatric acute myeloid leukemia through the miR-195/Myb axis

Background: Development of chemoresistance remains a major obstacle for pediatric acute myeloid leukemia (AML) management. Zinc finger antisense 1 (ZFAS1) is a novel tumor-related lncRNA that has been reported as an oncogene involved in the development of pediatric AML. The purpose of the present study was to investigate the role and underlying mechanism of ZFAS1 in AML chemoresistance. Methods: The expression levels of ZFAS1 and miR-195 were assessed by qRT-PCR and Myb expression was detected using western blotting. The CCK-8 assay was used to determine the IC50 value for adriamycin (ADR) and cell proliferation. Cell apoptosis was measured by flow cytometry. The targeted interaction between miR-195 and ZFAS1 or Myb was evaluated by the dual-luciferase reporter assay or RNA immunoprecipitation assay. Results: Our data revealed that ADR treatment induced ZFAS1 expression in pediatric AML. Silencing of ZFAS1 or Myb alleviated AML cell resistance to ADR in vitro. ZFAS1 directly targeted miR-195 and negatively modulated miR-195 expression. Myb was a direct target of miR-195. Moreover, the inhibitory effect of ZFAS1 silencing on ADR resistance of AML cells was mediated by miR-195 in vitro. Myb was involved in the regulation of the ZFAS1/miR-195 axis in ADR resistance of AML cells. Conclusion: Our data indicated that ZFAS1 silencing alleviated ADR resistance of AML cells in vitro through acting as a sponge for miR-195 and regulating Myb expression. Targeting ZFAS1 might be a promising therapeutic strategy for pediatric AML treatment.