| Summary: | Circular RNAs (circRNAs) have been shown to be closely linked to the tumorigenesis and treatment response of hematological malignancies. However, the biological functions and clinical implications of circRNAs in acute myeloid leukemia (AML) remain largely unknown. CircRNA microarray datasets were analyzed to screen differentially expressed circRNAs in AML patients. It was found that <i>circZBTB46</i> was significantly upregulated in AML patients and AML cells. Moreover, the expression of <i>circZBTB46</i> was associated with the stages of AML patients and showed high sensitivity and specificity for diagnosing AML. Silencing of <i>circZBTB46</i> inhibited AML cell proliferation and induced cell cycle arrest. Importantly, the depletion of <i>circZBTB46</i> notably increased ferroptosis and enhanced RSL3-induced ferroptosis in AML cells. Mechanistically, <i>circZBTB46</i> upregulated the expression of stearoyl-CoA desaturase 1 (SCD) possibly by acting as a miRNA sponge. Finally, the <i>circZBTB46</i> knockdown repressed the tumor growth of AML in vivo. In conclusion, <i>circZBTB46</i> protects AML cells from ferroptosis and promotes the proliferation by upregulating SCD, thus suggesting that <i>circZBTB46</i> may be a potential therapeutic target for AML.
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