Downregulation of histone methyltransferase SET8 inhibits progression of hepatocellular carcinoma

The expression of lysine methyltransferase SET8, which plays a role in the carcinogenesis of various human cancers through the monomethylation of histone H4 lysine 20 (H4K20), is linked to the prognosis of hepatocellular carcinoma (HCC). In this study, we conducted a functional analysis of SET8 to evaluate its impact on HCC progression. Knockdown of SET8 inhibited the proliferation, migration, and invasion of HCC cells, and also suppressed tumor growth in a human xenograft mouse model. Conversely, overexpression of SET8 reversed these effects, while treatment with the SET8 inhibitor UNC0379 produced results similar to SET8 knockdown. Additionally, drug sensitivity testing in SET8-siRNA-transfected HCC cells showed that docetaxel significantly inhibited cell growth, as demonstrated by the Cell Counting Kit-8 (CCK-8) assay. Gene expression microarray analysis revealed that the genes affected by SET8 knockdown were enriched in pathways related to tumorigenesis and metastasis. Our findings suggest that targeting SET8 could be a promising strategy for HCC therapy, as it not only inhibits the proliferation and invasion of HCC cells but also enhances their sensitivity to chemotherapy.