Figure 6.

Restoration of miR-424/503 expression and downregulation of KIF23 by demethylation.

A: BSP analysis of CpG islands methylation status in miR-424/503 cluster promoter region: Four CpG islands, from −4557 to −4150 (CpG island1), from −3383 to −2460 (CpG island2), from −2279 to −2177 (CpG island3) and from +50 to +503 (CpG island4) in miR-424/503 promoter region (the transcriptional start site was set as +1), were predicted via online software “methprimer”; Top part shows the coordinate active histone modification state from ENCODE; B: The statistical results of methylation levels of ovarian epithelial normal cell line and ovarian cancer cell lines; C-D: The statistical results of methylation levels of normal ovarian tissues and ovarian cancer tissues; E-F: Effects of decitabine (1 um, 20 um) on the miR-424-5p and miR-503-5p expression in HO8910PM (E) and HO8910 (F) cells. The mRNA and protein levels of KIF23 were analyzed after adding decitabine (1 um, 20 um) into HO8910PM (E) and HO8910 (F) cells; G: Proposed Regulatory Model for miR-424/503 cluster/KIF23 Axis in ovarian cancer Progression: Expression of miR-424-5p and miR-503-5p was silenced by hypermethylation of its promoter in ovarian cancer. MiR-424-5p and miR-503-5p inhibit cell proliferation and migration by directly targeting KIF23. (Data were shown by mean ± SEM from three independent experiments; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001, as compared to the control groups).