ARHGAP4 promotes leukemogenesis in acute myeloid leukemia by inhibiting DRAM1 signaling.
Yan QiMengjia HuChanghao HanJin WangFang ChenHui GuoYuanting SheMeijuan ZhangJing ZhangZhongyue ZhaoHuan XieSong WangMo ChenJun-Ping WangDongfeng ZengPublished in: Oncogene (2023)
Rho GTPase-activating protein 4 (ARHGAP4) is an important Rho family GTPase-activating protein that is strongly associated with the onset and progression of some tumors. We found that ARHGAP4 mRNA and protein are overexpressed in human acute myeloid leukemia (AML) patients and are associated with a poor prognosis. ARHGAP4 knockdown significantly impairs viability and colony formation capacity and induces apoptosis in AML cells. Further results demonstrate that ARHGAP4 deletion impairs AML progression in vivo. Interestingly, DRAM1 signaling is significantly activated in AML cells with ARHGAP4 knockdown. Our results also indicated that ARHGAP4 might function in AML cells by binding with p53 to inhibit DRAM1. Moreover, knockdown of DRAM1 rescues the defects of ARHGAP4 in AML cells. This newly described role of the ARHGAP4/DRAM1 axis in regulating AML progression may have important therapeutic implications.
Keyphrases
- acute myeloid leukemia
- induced apoptosis
- poor prognosis
- cell cycle arrest
- allogeneic hematopoietic stem cell transplantation
- signaling pathway
- end stage renal disease
- endoplasmic reticulum stress
- long non coding rna
- oxidative stress
- endothelial cells
- binding protein
- cell death
- chronic kidney disease
- ejection fraction
- small molecule
- acute lymphoblastic leukemia
- peritoneal dialysis
- mouse model