The RNA methylase FTO mediates circRNF220 demethylation, and circRNF220 binds to serine/arginine-rich splicing factor 1 to promote the progression of acute myeloid leukemia

Abstract Background: The key circular RNAs (circRNAs) and the molecular mechanisms by which they regulate the progression of acute myeloid leukemia (AML) in adults are unclear.Methods: We used a circRNA microarray to analyze the differentially expressed circRNAs in peripheral blood mononuclear cells of newly diagnosed adult AML patients. Reverse transcription-PCR, fluorescence in situ hybridization, Sanger sequencing, and ribonuclease R tests were used to examine circRNF220 loop formation and stability and its potential value in AML diagnosis. Cell Counting Kit-8, flow cytometry, and subcutaneous tumor assays were used to detect the effects of circRNF220 on the proliferation and apoptosis of the HL-60 and THP-1 cell lines. RNA antisense purification, methylated RNA immunoprecipitation, and RNA pull-down assays were used to identify circRNF220-binding proteins and microRNAs.Results: CircRNF220 was located in the cytoplasm and was more stable than linear RNF220. The area under the curve value of circRNF220 for the diagnosis of AML was 0.8314. Silencing circRNF220 expression inhibited the growth and promoted the early apoptosis of HL-60 and THP-1 cells. CircRNF220 had no competitive endogenous relationship with microRNAs. The RNA methylase FTO regulated the demethylation and expression of circRNF220. The RNA-binding protein serine/arginine-rich splicing factor 1 (SRSF1) and circRNF220 co-localized in the cytoplasm, and circRNF220 promoted SRSF1 expression. Furthermore, silencing circRNA220 reduced the tumorigenicity of AML cells in vivo.Conclusions: CircRNF220 is a potential biomarker for the diagnosis of adult AML. FTO mediates circRNF220 demethylation. and circRNF220 binds to SRSF1 to promote the progression of AML.