STAT3 and AKT signaling pathways mediate oncogenic role of NRSF in hepatocellular carcinoma  

作　　者：Ming Ma Yunhe Zhou Ruilin Sun Jiahao Shi Yutong Tan Hua Yang Mengjie Zhang Ruling Shen Leon Xu Zhugang Wang Jian Fei 

机构地区：[1]School of Life Science and Technology,Tongji University,Shanghai 200092,China [2]Sports and Health Research Center,Tongji University,Shanghai 200092,China [3]Shanghai Engineering Research Center for Model Organisms,SMOC,Shanghai 201318,China [4]Joint Laboratory for Model Organism,Shanghai Laboratory Animal Research Center,Shanghai 201203,China

出　　处：《Acta Biochimica et Biophysica Sinica》2020年第10期1063-1070,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National NaturalScience Foundation of China(Nos.81572776 and 31401019);the Science and Technology Commission of Shanghai Municipality(No.19DZ2280500);the Science and Technology Commission of Pudong New District Shanghai Municipality(No.PKF2015-C03).

摘　　要：Neuron-restrictive silencer factor(NRSF)is a zinc finger protein that acts as a negative transcriptional regulator by recruiting histone deacetylases and other co-factors.It plays a crucial role in nervous system development and is recently reported to be involved in tumorigenesis in a tumor type-dependent manner;however,the role of NRSF in hepatocellular carcinoma(HCC)tumorigenesis remains unclear.Here,we found that NRSF expression was up-regulated in 27 of 49 human HCC tissue samples examined.Additionally,mice with conditional NRSF-knockout in the liver exhibited a higher tolerance against diethylnitrosamine(DEN)-induced acute liver injury and were less sensitive to DEN-induced HCC initiation.Our results showed that silencing NRSF in HepG2 cells using RNAi technology significantly inhibited HepG2 cell proliferation and severely hindered their migration and invasion potentials.Our results demonstrated that NRSF plays a pivotal role in promoting DEN-induced HCC initiation via a mechanism related to the STAT3 and AKT signaling pathways.Thus,NRSF could be a potential therapeutic target for treating human HCC.

关 键 词：hepatocellular carcinoma HEPG2 NRSF proliferation STAT3 

分 类 号：Q51[生物学—生物化学] R73[医药卫生—肿瘤]