Histone methyltransferase EZH2 epigenetically affects CCNA1 expression in acute myeloid leukemia

Cyclin A1 (CCNA1) is an alternative A-type cyclin that is expressed in acute myeloid leukemia (AML). However, its functions in AML cell chemoresistance, an important cause for mortality, are incompletely understood. The purpose of this study was to expound the role and potential mechanism of CCNA1 in AML cell chemoresistance. Upregulation of CCNA1 promoted resistance of AML cells to PKC412, AC220, and AraC. Mechanistically, it was confirmed that CCNA1 transcription was negatively regulated by forkhead box A2 (FOXA2), and the downregulation of FOXA2 promoted chemoresistance in AML cells. Moreover, the promoter sequence of CCNA1 has a significant H3K27me3 modification. Enhancer of zeste homolog 2 (EZH2) enhanced H3K27me3 modification of CCNA1 promoter to inhibit CCNA1 expression, thus promoting sensitivity of AML cells to drugs. Taken together, these findings lead to deeper insights into the mechanism of AML cell chemo-sensitivity by inhibiting CCNA1 at the transcriptional level. •Amplification of CCNA1 associates with poor prognosis and chemoresistance in AML.•Amplification of CCNA1 induces drug resistance in AML in vitro and in vivo.•CCNA1 is transcriptionally regulated by FOXA2.•EZH2 promotes drug sensitivity in AML cells through inhibition of CCNA1 expression.•Targeting CCNA1 may be a viable approach to overcome chemoresistance in AML patients.