USP8 regulates liver cancer progression via the inhibition of TRAF6-mediated signal for NF-κB activation and autophagy induction by TLR4.
USP8 regulates liver cancer progression via the inhibition of TRAF6-mediated signal for NF-κB activation and autophagy induction by TLR4.
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DOI：
10.1016/j.tranon.2021.101250
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发表时间：
2022-01
影响因子：
5
通讯作者：
Lee KY
中科院分区：
文献类型：
--
作者：
Kim MJ;Choi B;Kim JY;Min Y;Kwon DH;Son J;Lee JS;Lee JS;Chun E;Lee KY
USP的细胞活性在功能上与癌症进展有关。USP 8负调节TRAF 6介导的NF-κB和自噬信号。USP 8 KO SK-HEP-1细胞揭示了体内和体外癌症进展的增加。TCGA和转录组数据支持USP 8在肝癌中的功能作用。在此，我们旨在阐明泛素特异性蛋白酶8（USP 8）通过TRAF 6介导的信号参与肝癌进展的分子和细胞机制。USP 8诱导TRAF 6、TAB 2、TAK 1、p62和BECN 1的去泛素化，这些是NF-κB活化和自噬诱导的关键作用。值得注意的是，USP 8 mRNA低表达的LIHC患者的生存时间明显缩短，而其他18种癌症患者的生存时间无显著差异。重要的是，对LIHC的TCGA数据分析和对USP 8敲除（USP 8 KO）SK-HEP-1细胞的转录组分析揭示了USP 8与TRAF 6、TAB 2、TAK 1、p62和BECN 1之间的显著相关性，并增强了NF-κ B依赖性和自噬相关的癌症进展/转移相关基因对LPS刺激的响应。此外，USP 8 KO SK-HEP-1细胞显示通过TLR 4刺激的癌症迁移和侵袭增加，并且在异种移植的NSG小鼠中致瘤性和转移显著增加。结果表明，USP 8通过调节TRAF 6介导的NF-κB活化和自噬诱导的信号而与LIHC进展负相关。我们的研究结果提供了有用的见解LIHC的发病机制的癌症进展。
The cellular activity of USPs is functionally implicated in cancer progression. USP8 negatively regulates the TRAF6-mediated signals for NF-κB and autophagy. USP8KO SK-HEP-1 cells reveal increases of cancer progression in vivo and in vitro. TCGA and transcriptome data support the functional role of USP8 in liver cancers. Herein, we aimed to elucidate the molecular and cellular mechanism in which ubiquitin-specific protease 8 (USP8) is implicated in liver cancer progression via TRAF6-mediated signal. USP8 induces the deubiquitination of TRAF6, TAB2, TAK1, p62, and BECN1, which are pivotal roles for NF-κB activation and autophagy induction. Notably, the LIHC patient with low USP8 mRNA expression showed markedly shorter survival time, whereas there was no significant difference in the other 18-human cancers. Importantly, the TCGA data analysis on LIHC and transcriptome analysis on the USP8 knockout (USP8KO) SK-HEP-1 cells revealed a significant correlation between USP8 and TRAF6, TAB2, TAK1, p62, and BECN1, and enhanced NF-κB-dependent and autophagy-related cancer progression/metastasis-related genes in response to LPS stimulation. Furthermore, USP8KO SK-HEP-1 cells showed an increase in cancer migration and invasion by TLR4 stimulation, and a marked increase of tumorigenicity and metastasis in xenografted NSG mice. The results demonstrate that USP8 is negatively implicated in the LIHC progression through the regulation of TRAF6-mediated signal for the activation of NF-κB activation and autophagy induction. Our findings provide useful insight into the LIHC pathogenesis of cancer progression.
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影响因子：
--
作者：
Bhutia, Sujit K.;Mukhopadhyay, Subhadip;Sinha, Niharika;Das, Durgesh Nandini;Panda, Prashanta Kumar;Patra, Samir K.;Maiti, Tapas K.;Mandal, Mahitosh;Dent, Paul;Wang, Xiang-Yang;Das, Swadesh K.;Sarkar, Devanand;Fisher, Paul B.
通讯作者：
Fisher, Paul B.
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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