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 Ara-C. 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.

Automated summary

This study elucidates that upregulation of CCNA1 in AML cells promotes chemoresistance, while downregulation of FOXA2 and the action of EZH2 increase sensitivity of AML cells to drugs.