Dysregulated YAP1/Hippo Pathway Contributes to Doxorubicin (ADM) Resistance in Acute Myeloid Leukemia (AML)

Abstract

Background: Dysregulated Yes-associated protein 1 (YAP1) is closely associated with cancer progression and chemo-resistance. We aim to explore the role of YAP1/Hippo pathway in regulating doxorubicin (ADM)-resistance in acute myeloid leukemia (AML). Methods: In this study, we established two ADM-resistant cell lines (THP-1/ ADM and K562/ ADM). Then cell viability and apoptosis were detected by MTT assay and FCM assay, respectively. Real time PCR were performed to examine the expression of genes in the AML/ADM cells and the clinic BM samples. The levels of all related proteins were examined by Western blot. Results: We found that the YAP1 and its downstream target genes, including EGFR, SOX2, and OCT4, were associated with ADM-resistance, evidenced by the increased expression in ADM-resistant AML/ADM cells and clinical BM specimens. Additionally, YAP1 ablation enhanced the promoting effects of ADM treatment on cell death in AML/ADM cells. Conversely, YAP1 increased ADM-a resistance in the original ADM-sensitive AML cells. These results may provide important new insights into understanding this role of YAP1 regulates AML resistance by affecting CSCs characteristics. Conclusion: In summary, we evidenced that the dysregulated YAP1/Hippo pathway influenced ADM-resistance in AML. YAP1 might be novel biomarkers for treatment of drug-resistance in AML.