PRDM8 exhibits antitumor activities toward hepatocellular carcinoma by targeting NAP1L1

被引：40

作者：

Chen, Zhiqiang ^{[1
,2
]}

Gao, Wen ^{[3
]}

Pu, Liyong ^{[1
,2
]}

Zhang, Long ^{[1
,2
]}

Han, Guoyong ^{[1
,2
]}

Zuo, Xueliang ^{[1
,2
]}

Zhang, Yao ^{[1
,2
]}

Li, Xiangcheng ^{[1
,2
]}

Shen, Hongbing ^{[4
,5
]}

Wu, Jindao ^{[1
,2
,4
]}

Wang, Xuehao ^{[1
,2
]}

机构：

[1] Nanjing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China

[2] Natl Hlth & Family Planning Commiss, Key Lab Living Donor Liver Transplantat, Nanjing, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Dept Oncol, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China

[4] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China

[5] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Dept Epidemiol & Biostat,Sch Publ Hlth, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Jiangsu, Peoples R China

来源：

HEPATOLOGY | 2018年 / 68卷 / 03期

基金：

中国国家自然科学基金;

关键词：

DNA METHYLATION; EXPRESSION; DIFFERENTIATION; PATHWAY; FAMILY; GENES;

D O I：

10.1002/hep.29890

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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. (Hepatology 2018).

引用

页码：994 / 1009

页数：16

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