Figure 8. Schematic illustration of the NOR1-FOXA1/HDAC2-SLUG regulatory network in the EMT process of NPC.

In normal nasopharyngeal epitheliums, high levels of NOR1 expression lead to optimal expression of FOXA1; FOXA1 then translocates to the nucleus, recruits HDAC2, and binds to the slug promoter region, resulting in de-acetylation and secondary tri-methylation of Slug-associated H3K9. The transcription of Slug is repressed and Slug protein levels are decreased, so the cells are maintained as epithelial cells. During NPC development, NOR1 is silenced by DNA hypermethylation or deletions, which in turn results in a decrease in the expression of FOXA1 and HDAC2, thus removing the inhibitory effect on the transcription of slug. The transcription of slug is activated and Slug protein production is upregulated, subsequently leading to the Slug-induced EMT process. HMTs, histone methyl transferases. JMJD, Jumonji domain–containing protein histone demethylases. HATs, histone acetyltransferases.