Fig. 8.

DHX9 is required for p65 and RNA Pol II recruitment to the promoters of NF-κB-dependent genes. A–C ChIP-qPCR analysis for DHX9, p65 or RNA Pol II occupancy at the promoter of BIRC5 A, SNAI1 B or ACTB C in HCT116 cells stably expressed DHX9 cDNA or shDDR1 constructs. All data in bar graphs were shown as mean ± SEM from three independent experiments and analyzed by one-way ANOVA, post hoc intergroup comparisons, Tukey’s test. D A proposed working model of DHX9 in orchestrating the malignant phenotypes of CRC. On one hand, DHX9 enhances p65 phosphorylation, promotes p65 nuclear translocation to facilitate NF-κB-mediated transcriptional activity. On the other hand, DHX9 interacts with p65 and RNA Pol II and is necessary to recruit p65 and RNA Pol II to the NF-κB-dependent promoters to activate downstream gene transcription, including CXCL8, CCND1, BIRC5 and SNAI1. Enhanced CXCL8, Cyclin D1 and Survivin expression contributes to lower apoptosis and promote proliferation in CRC cells; the strengthened expression of Snail increases the capability of migration and invasion, and ultimately facilities liver colonization and metastasis in CRC