CircNR3C1 promotes acute lymphoblastic leukemia progression via the MSI2/ENO1/RPS3 axis

Abstract Acute lymphoblastic leukemia is a hematological malignancy characterized by the uncontrolled proliferation of immature lymphoid cells, but the role of circNR3C1 in acute lymphoblastic leukemia is not fully elucidated. In this study, expression levels of circNR3C1, RPS3, ENO1, and MSI2 were assessed in acute lymphoblastic leukemia cell lines and normal bone marrow mononuclear cells using RT-qPCR and Western blotting. Co-immunoprecipitation, RNA immunoprecipitation, RNA pull-down, and protein stability analyses were performed to investigate interactions between circNR3C1, MSI2, ENO1, and RPS3. A xenograft mouse model was utilized to assess the impact of circNR3C1 on tumor growth. The results showed that circNR3C1 expression was significantly upregulated in acute lymphoblastic leukemia cells compared to normal bone marrow mononuclear cells. Knockdown of circNR3C1 suppressed proliferation and induced apoptosis in acute lymphoblastic leukemia cells. CircNR3C1 positively regulated RPS3 expression by enhancing the stability of ENO1 mRNA through interaction with MSI2. ENO1 is bound to RPS3, increasing its protein stability. Overexpression of MSI2 or RPS3 reversed the inhibitory effects of circNR3C1 knockdown on cell proliferation and survival. These findings indicate that circNR3C1 promotes acute lymphoblastic leukemia cell proliferation and inhibits apoptosis by interacting with MSI2 to stabilize ENO1 mRNA, leading to upregulation of ENO1 and RPS3. The circNR3C1/MSI2/ENO1/RPS3 axis represents a novel regulatory pathway contributing to acute lymphoblastic leukemia progression and offers potential therapeutic targets for treatment.