Combining the results of motif analyses with the RNA-seq, we excluded the genes whose roles in HCC have been well-established and the ones with few motifs, and conducted ChIP experiments to verify the direct regulatory effect, as well as the specific binding between KLF8 and several apoptotic-related genes (KLF8 v.s. IgG in LM3 and Huh-7 cells: P < 0.001 and 0.003 for HMGA2; both P < 0.001 for MMP7; P = 0.004 and 0.056 for CAP1) (Fig. 4c–e; Additional file 2: Table S2). Here, MMP7 is linked to hepatocellular carcinoma.