Fig. 6: MARK3 regulate AP-1 and Hippo signaling target genes.

a, b ATAC-seq analysis. Ranking of the most differential motifs in response to MARK3 overexpression in OVCAR3 (a) and 293T (b) cells. In both cell lines, the activities of transcription factors, which make up the AP-1 complex, such as the Jun family and Fos family, are significantly decreased. Jaspar core non-redundant motifs are included in this motif enrichment analysis. c Immunoblotting shows that MARK3 overexpression in OVCAR3 and 293T cells decreases the phosphorylation of c-Jun, indicating that MARK3 antagonizes the activity of the AP-1 complex. d RNA-seq analysis. Representative AP-1 target genes are downregulated upon MARK3 overexpression. Error bars represent mean ± SD of three biological replicates. Statistical analysis was performed using unpaired Student’s t-test (*P < 0.01). e, f RNA-seq analysis. Volcano plot demonstrates that MARK3 overexpression in OVCAR3 cells downregulates both Hippo signature genes (e) and YAP/TAZ target genes (f). g Immunoblotting shows that MARK3 overexpression in OVCAR3 cells inhibits nuclear translocation of YAP and decreases the protein expression of Hippo signaling target genes, such as CTGF and MYC. h, i Mouse xenograft experiment using MARK3 DOX-inducible OVCAR3 cells. The growth curves of the tumor volume (h) and the bodyweight (i) distribution of mouse xenografts. n = 10 in DOX-negative group and n = 10 in DOX-positive group. Error bars represent mean ± SD. Statistical analysis was performed using an unpaired Student’s t-test. j Representative images of CD31 immunohistochemistry of mouse xenografts with or without DOX treatment.