LncRNA AC098613.1 promotes acute myeloid leukemia cell differentiation through CDC5L/ADAP1/NRD1 axis.

Recently evidence has suggested that long non-coding RNAs (lncRNAs) play a pivotal role in the prognosis and treatment of leukemia. However, studies on their use in differentiation therapy of acute myeloid leukemia (AML) remain scarce. In this study, we found that AC098613.1 was significantly increased in differentiated THP-1 cells, while its expression was significantly lower in AML patients. Moreover, AC098613.1 overexpression inhibited proliferation and induced differentiation of THP-1 and HL-60 cells. Mechanistically, we found that AC098613.1 targeted cell division cycle 5-like protein (CDC5L) to increase its stability, thereby enhancing its abundance and nuclear localization, and promoted the transcription of ADP-ribosylation factor GTPase activating protein with dual PH domains 1 (ADAP1) and the expression of nardilysin (encoded by NRD1), which ultimately induced the differentiation of AML cells. We further demonstrated in vivo that AC098613.1 overexpression significantly inhibited tumor growth by affecting the stability of CDC5L and regulating the expression of ADAP1, NRD1 and cyclin-dependent kinase 1 (CDK1). The research demonstrates that AC098613.1 promotes AML cell differentiation by regulating the CDC5L/ADAP1/NRD1 axis, providing a new target for AML differentiation therapy.