Knockdown of LncRNA-UCA1 suppresses chemoresistance of pediatric AML by inhibiting glycolysis through the microRNA-125a/hexokinase 2 pathway.

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