Abstract
Nucleus accumbens-associated protein 1 (NACC1) regulates various types of biological processes. It is a transcription factor associated with cancer. NACC1 is overexpressed in many human malignancies and can regulate the progression, metastasis, and drug resistance of cancer cells. However, its precise role in acute myeloid leukemia (AML) remains unknown. This study aimed to unravel the basic mechanism of NACC1 in AML. Our findings demonstrated that NACC1 is immensely expressed in AML cells. Lentiviral vector-mediated knockdown of NACC1 inhibited the PI3K/AKT signaling pathway. Simultaneously, NACC1 knockdown promoted apoptosis, suppressed the proliferative capacity of AML cells, and resulted in cell cycle arrest during the G0/G1 phase. Additionally, A disintegrin and metalloproteinase 9 (ADAM9) was markedly expressed in AML cells. NACC1 regulated ADAM9 expression. ADAM9 expression was also downregulated after NACC1 knockdown. Concurrently, ADAM9 knockdown affected the activity of AML cells by decelerating the growth rate, promoting apoptosis, and blocking cell cycle progression. In addition, the AKT activator SC79 restored the inhibited cell proliferation after NACC1 knockdown and ADAM9 knockdown. In conclusion, our study suggested that the NACC1/ADAM9/PI3K/AKT axis is crucial for sustaining the survival of AML cells, indicating that NACC1 may be a viable target for treating AML.