Fig. 7: Model for the functional mechanism of the HCC risk-associated enhancer variant rs73613962 in the intronic region of PRMT7.

The region containing the HCC susceptibility locus rs73613962 inside the intronic region of PRMT7 is identified as an enhancer that can regulate PRMT7 expression through the interaction with its promoter. Transcription factor HNF4A prefers to bind to the risk allele G over the non-risk allele T, which leads to the upregulated expression of PRMT7. Under this condition, the H4R3me2s modification on the promoter region of the genes in the p53 signaling pathway is elevated; thereby, the RNA and protein level is reduced. As a result, cells are induced to have enhanced malignant phenotypes, with higher proliferation rate and migration and invasion abilities.