Hotair Suppresses Pten Via Dnmt3b And Confers Drug Resistance In Acute Myeloid Leukemia

ObjectiveHOTAIR has been well reported to be involved in the drug resistance of many diseases. This study aims to explore the possible implication of HOTAIR in doxorubicin (ADM) resistance in acute myeloid leukemia (AML).MethodsExpressions of HOTAIR and PTEN in bone marrows of patient with newly diagnosed AML and relapsed/refractory AML and of healthy controls were determined by RT-qPCR. The half maximal inhibitory concentration (IC50) was calculated after AML-ADM-sensitive cells HL60 and AML-ADM-resistant cells HL60/ADM cells were treated by ADM. The IC50 of HL60/ADM to ADM dosage was determined by CCK-8. After cells were transfected with Sh-HOTAIR, pcDNA3.1-HOTAIR or pcDNA3.1-PTEN, cell biology of HL60/ADM cells was detected by flow cytometry, clone formation assay. The methylation of PTEN was determined by Methylmion-specific PCR and Bisulfite Genomic Sequence.ResultsPatient with relapsed/refractory AML had the highest HOTAIR and the lowest PTEN expression, followed by that in newly diagnosed AML patients and then healthy controls. After ADM treatment, cell viability and IC50 were enhanced in HL60/ADM cell when compared with HL60 cells. Up-regulated HOTAIR and down-regulated PTEN were found in HL60/ADM cells. Cell transfection with sh-HOTAIR or pcDNA3.1-PTEN leads to increased ADM sensitivity, apoptosis rate as well as decreased IC50 and cell clones, while those expression patterns can be reversed by co-transfection of pcDNA3.1-PTEN and pcDNA3.1-HOTAIR. Methylation was observed in the promoter of PTEN. HOTAIR can positively regulate DNMT3b.ConclusionHOTAIR suppresses PTEN through up-regulating DNMT3b-dependent way and confers ADM resistance in AML.