Abstract

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.

中文翻译：

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STAT3和AKT信号通路介导NRSF在肝细胞癌中的致癌作用。

摘要

神经元限制性沉默因子（NRSF）是一种锌指蛋白，通过募集组蛋白脱乙酰基酶和其他辅助因子而充当负转录调节因子。它在神经系统发育中起着至关重要的作用，最近据报道以肿瘤类型依赖性的方式参与肿瘤发生。然而，NRSF在肝细胞癌（HCC）肿瘤发生中的作用仍不清楚。在这里，我们发现在49个人类HCC组织样本中的27个中，NRSF表达上调。此外，肝脏中有条件的NRSF基因敲除的小鼠对二乙基亚硝胺（DEN）诱导的急性肝损伤表现出更高的耐受性，并且对DEN诱导的HCC起始敏感性较低。我们的结果表明，使用RNAi技术沉默HepG2细胞中的NRSF可以显着抑制HepG2细胞的增殖，并严重阻碍其迁移和侵袭潜能。我们的结果表明，NRSF通过与STAT3和AKT信号通路相关的机制在促进DEN诱导的HCC起始中起关键作用。因此，NRSF可能是治疗人类HCC的潜在治疗靶标。