1. ATPR triggers acute myeloid leukaemia cells differentiation and cycle arrest via the RARα/LDHB/ERK‐glycolysis signalling axis
- Author
-
Xiao-Qin Peng, Xiao-Lin Xu, Feihu Chen, Hao Chen, Yan Du, Yan Li, Mei-ju Zhang, Yubin Feng, and Lan-lan Li
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,4‐Amino‐2‐Trifluoromethyl‐Phenyl Retinate (ATPR) ,Retinoic acid ,Down-Regulation ,Raf/MEK/ERK signalling ,Peripheral blood mononuclear cell ,Viral vector ,Small hairpin RNA ,03 medical and health sciences ,chemistry.chemical_compound ,Retinoids ,0302 clinical medicine ,Acute myeloid leukaemia (AML) ,hemic and lymphatic diseases ,Cell Line, Tumor ,Humans ,Glycolysis ,All‐trans retinoic acid (ATRA) ,Extracellular Signal-Regulated MAP Kinases ,neoplasms ,Cell Proliferation ,Mitogen-Activated Protein Kinase Kinases ,Gene knockdown ,L-Lactate Dehydrogenase ,Gene Expression Regulation, Leukemic ,Retinoic Acid Receptor alpha ,Cell Differentiation ,Cell Biology ,Original Articles ,Cell Cycle Checkpoints ,Lactate dehydrogenase B (LDHB) ,Isoenzymes ,Leukemia, Myeloid, Acute ,030104 developmental biology ,chemistry ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Original Article ,raf Kinases ,Signal Transduction - Abstract
Acute myeloid leukaemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. 4‐Amino‐2‐trifluoromethyl‐phenyl retinate (ATPR), a novel all‐trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show superior anticancer effect compared with ATRA on various cancers. However, its potential effect on AML remains largely unknown. Lactate dehydrogenase B (LDHB) is the key glycolytic enzyme that catalyses the interconversion between pyruvate and lactate. Currently, little is known about the role of LDHB in AML. In this study, we found that ATPR showed antileukaemic effects with RARα dependent in AML cells. LDHB was aberrantly overexpressed in human AML peripheral blood mononuclear cell (PBMC) and AML cell lines. A lentiviral vector expressing LDHB‐targeting shRNA was constructed to generate a stable AML cells with low expression of LDHB. The effect of LDHB knockdown on differentiation and cycle arrest of AML cells was assessed in vitro and vivo, including involvement of Raf/MEK/ERK signalling. Finally, these data suggested that ATPR showed antileukaemic effects by RARα/LDHB/ ERK‐glycolysis signalling axis. Further studies should focus on the underlying leukaemia‐promoting mechanisms and investigate LDHB as a therapeutic target.
- Published
- 2020