ARHGAP4 promotes leukemogenesis in acute myeloid leukemia by inhibiting DRAM1 signaling

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.

Automated summary

Rho GTPase-activating protein 4 (ARHGAP4) is overexpressed in human acute myeloid leukemia (AML) patients and is associated with a poor prognosis. Knockdown of ARHGAP4 impairs viability and induces apoptosis in AML cells, while ARHGAP4 deletion impairs AML progression in vivo. The ARHGAP4/DRAM1 axis plays a crucial role in regulating AML progression.