文章：

肿瘤抑制因子SOCS1降低肝细胞癌对氧化应激的耐受性

The Tumor Suppressor SOCS1 Diminishes Tolerance to Oxidative Stress in Hepatocellular Carcinoma

原文发布日期：10 January 2024

DOI: 10.3390/cancers16020292

类型: Article

开放获取: 是

英文摘要：

SOCS1 is a tumor suppressor in hepatocellular carcinoma (HCC). Recently, we showed that a loss of SOCS1 in hepatocytes promotes NRF2 activation. Here, we investigated how SOCS1 expression in HCC cells affected oxidative stress response and modulated the cellular proteome. Murine Hepa1-6 cells expressing SOCS1 (Hepa-SOCS1) or control vector (Hepa-Vector) were treated with cisplatin or tert-butyl hydroperoxide (t-BHP). The induction of NRF2 and its target genes, oxidative stress, lipid peroxidation, cell survival and cellular proteome profiles were evaluated. NRF2 induction was significantly reduced in Hepa-SOCS1 cells. The gene and protein expression of NRF2 targets were differentially induced in Hepa-Vector cells but markedly suppressed in Hepa-SOCS1 cells. Hepa-SOCS1 cells displayed an increased induction of reactive oxygen species but reduced lipid peroxidation. Nonetheless, Hepa-SOCS1 cells treated with cisplatin ort-BHP showed reduced survival.GCLC, poorly induced in Hepa-SOCS1 cells, showed a strong positive correlation withNFE2L2and an inverse correlation withSOCS1in the TCGA-LIHC transcriptomic data. A proteomic analysis of Hepa-Vector and Hepa-SOCS1 cells revealed that SOCS1 differentially modulated many proteins involved in diverse molecular pathways, including mitochondrial ROS generation and ROS detoxification, through peroxiredoxin and thioredoxin systems. Our findings indicate that maintaining sensitivity to oxidative stress is an important tumor suppression mechanism of SOCS1 in HCC.

摘要翻译： 

SOCS1是肝细胞癌（HCC）中的一种肿瘤抑制因子。近期，我们发现肝细胞中SOCS1的缺失会促进NRF2的激活。本研究旨在探讨HCC细胞中SOCS1的表达如何影响氧化应激反应并调控细胞蛋白质组。我们使用顺铂或叔丁基过氧化氢（t-BHP）处理表达SOCS1的小鼠Hepa1-6细胞（Hepa-SOCS1）及对照载体细胞（Hepa-Vector），并评估了NRF2及其靶基因的诱导情况、氧化应激水平、脂质过氧化程度、细胞存活率以及细胞蛋白质组谱。结果显示，Hepa-SOCS1细胞中NRF2的诱导显著降低。NRF2靶基因的mRNA和蛋白表达在Hepa-Vector细胞中呈现差异性诱导，而在Hepa-SOCS1细胞中则明显受到抑制。Hepa-SOCS1细胞表现出活性氧物种诱导增加，但脂质过氧化水平降低。然而，经顺铂或t-BHP处理的Hepa-SOCS1细胞存活率下降。在TCGA-LIHC转录组数据中，在Hepa-SOCS1细胞中诱导较差的GCLC与NFE2L2呈强正相关，而与SOCS1呈负相关。对Hepa-Vector和Hepa-SOCS1细胞的蛋白质组学分析表明，SOCS1通过过氧化物氧还蛋白和硫氧还蛋白系统，差异性调控了涉及多种分子途径的众多蛋白质，包括线粒体ROS生成和ROS解毒过程。我们的研究结果表明，维持对氧化应激的敏感性是SOCS1在HCC中发挥肿瘤抑制功能的重要机制。

原文链接：

The Tumor Suppressor SOCS1 Diminishes Tolerance to Oxidative Stress in Hepatocellular Carcinoma