PRDM8 exhibits antitumor activities toward hepatocellular carcinoma by targeting NAP1L1

Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. PRDI‐BF1 and RIZ homology domain containing 8 (PRDM8) is a key regulator in neural development and testis steroidogenesis; however, its role in liver carcinogenesis remains to be investigated. In this study, PRDM8 was found to be down‐regulated in HCC, which was linked with shorter recurrence‐free survival. Lentiviral‐based overexpression and knockdown approaches showed that PRDM8 inhibited HCC cell proliferation, migration, and invasion. PRDM8 caused G1/S cell cycle arrest and induced apoptosis. An in vivo tumor model confirmed the antitumor role of PRDM8 in HCC growth and metastasis. Mechanistic study showed that PRDM8 suppressed the PI3K/AKT/mTOR signaling cascade through the regulation of nucleosome assembly protein 1‐like 1 (NAP1L1). Conclusion : PRDM8 as a functional tumor suppressor is frequently down‐regulated in HCC. Through regulating NAP1L1, PRDM8 inhibits PI3K/AKT/mTOR signaling in HCC. PRDM8 is a potential target for therapies of HCC. (H epatology 2018).