DNA methylation-regulated DDX27 promotes colorectal cancer progression through EZH2

To investigate the oncogenic role of DDX27 in colorectal cancer (CRC) and its regulation of EZH2.

DDX27 expression and prognostic value were analyzed using TCGA. qRT-PCR was performed on 30 paired CRC and adjacent tissues; DDX27 levels in CRC cell lines (HCT116, HT-29, SW480, SW620, HCT-8) were assessed by qRT-PCR and Western blot. Methylation-specific PCR evaluated CpG methylation of the DDX27 promoter and the effect of 5-azacytidine (5-AZ). Functional assays (CCK-8, flow cytometry, wound healing, transwell) examined proliferation, apoptosis, migration and invasion after DDX27 knockdown (si-DDX27). RNA-seq and bioinformatics analyses, together with Western blot assays, were used to identify downstream effectors. Luciferase reporter assays tested EZH2 promoter activity following DDX27 depletion. Rescue experiments overexpressed EZH2 in DDX27-silenced cells. In vivo, HCT116 cells with DDX27 shRNA or control shRNA were implanted in mice and tumor EZH2 was evaluated by IHC.

DDX27 was upregulated in CRC and correlated with poorer prognosis. Promoter hypomethylation was observed and 5-AZ increased DDX27 expression. DDX27 knockdown inhibited proliferation, migration and invasion and increased apoptosis. Silencing DDX27 reduced EZH2 protein and significantly lowered EZH2 promoter luciferase activity. EZH2 overexpression partially rescued the anti-tumor effects of DDX27 silencing. In vivo DDX27 depletion suppressed tumor growth and reduced EZH2 expression.

DDX27 promotes CRC progression partly via transcriptional upregulation of EZH2; promoter hypomethylation contributes to DDX27 overexpression. Targeting the DDX27-EZH2 axis may be therapeutically valuable.