BACKGROUND & AIMS: The inhibition of epigenetic regulators activates endogenous retrovirus (ERV) expression, which can stimulate a viral mimicry response in cancer cells. ERV elements are aberrantly expressed in hepatocellular carcinoma (HCC)
however, the expression of ERVs regulated by histone modifications and their clinical significance in HCC remain unclear. Here, we identified specific human endogenous retrovirus (HERV) elements epigenetically suppressed by the histone methyltransferase SETDB1 in HCC. METHODS: The Cancer Genome Atlas (TCGA) dataset was analyzed to identify HERV elements based on RESULTS: TCGA analysis revealed an inverse correlation between CONCLUSIONS: The suppression of four novel HERV elements by SETDB1 serves as a prognostic marker in HCC. Activation of these SETDB1-regulated HERVs could represent a promising therapeutic strategy for HCC. IMPACT AND IMPLICATIONS: An inverse relationship between retroelements including human endogenous retrovirus (HERV) elements and