LAUSR

Dysregulation of lncRNAs is implicated in chemoresistance in varieties of tumor including acute myeloid leukemia (AML). LncRNA urothelial carcinoma‐associated 1 (UCA1) was reported to play an oncogenic role in AML. However, whether UCA1 was involved in chemoresistance in pediatric AML remains unclear. UCA1 expression in AML patients after adriamycin (ADR)‐based chemotherapy and ADR‐resistant AML cells was examined by qRT‐PCR. The effects of UCA1 on the cytotoxicity of ADR and glycolysis were evaluated by MTT assay and measuring the glucose consumption and lactate production in HL60 and HL60/ADR cells, repectively. The protein levels of hypoxia‐inducible factor 1α (HIF‐1α) and hexokinase 2 (HK2) were determined by Western blot. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm the relationships between UCA1, HK2, and miR‐125a. We found that UCA1 expression was upregulated following ADR‐based chemotherapy. Knockdown of UCA1 increased the cytotoxic effect of ADR and inhibited HIF‐1α‐dependent glycolysis in ADR‐resistant AML cells. Additionally, UCA1 functioned as a ceRNA of miR‐125a by directly binding to miR‐125a. HK2, a target of miR‐125a, was positively regulated by UCA1 in HL60 and HL60/ADR cells. More notably, UCA1 overexpression overturned miR‐125‐mediated inhibition on HIF‐1α‐dependent glycolysis in HL60 and HL60/ADR cells. Furthermore, 2‐deoxy‐glucose (2‐DG) exposure inhibited HIF‐1α‐dependent glycolysis, and attenuated UCA1‐induced increase of chemoresistance in HL60 and HL60/ADR cells. We conclude that knockdown of UCA1 plays a positive role in overcoming the chemoresistance of pediatric AML, through suppressing glycolysis by the miR‐125a/HK2 pathway, contributing to a better understanding of the molecular mechanism of chemoresistance in AML.