To explore whether miR-337-3p directly binds the MMP-14 promoter, lysates from miR-337-3p over-expressing NB cells were pretreated with RNase H or RNase A. As shown in Figure 4E, RNase H treatment, but not RNase A treatment, prevented the NB cells from increased enrichment of AGO2, EZH2, H3K27me3, and H3K9me2, and decreased binding of RNA Pol II and Sp1 on the MMP-14 promoter induced by miR-337-3p, indicating the direct binding of miR-337-3p on MMP-14 promoter. The gene discussed is SP1; the disease is neuroblastoma.