PARP6 suppresses the proliferation and metastasis of hepatocellular carcinoma by degrading XRCC6 to regulate the Wnt/β-catenin pathway.
PARP6 suppresses the proliferation and metastasis of hepatocellular carcinoma by degrading XRCC6 to regulate the Wnt/β-catenin pathway.
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PARP6 通过降解 XRCC6 调节 Wnt/β-catenin 通路来抑制肝细胞癌的增殖和转移。
DOI：
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发表时间：
2020-07
影响因子：
5.3
通讯作者：
Shimamoto Fumio
中科院分区：
文献类型：
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作者：
Tang Bo;Zhang Yi;Wang Wei;Qi Guangying;Shimamoto Fumio
PARP 6属于单-ADP-核糖基转移酶家族，并已被证明参与一些肿瘤的发生和发展。然而，PARP 6在肝细胞癌（HCC）发展中的作用仍有待充分阐明。在目前的研究中，我们证明PARP 6在HCC细胞中以低水平表达，并且与肿瘤分化程度呈负相关。此外，在体外和体内测定中，沉默PARP 6导致HCC细胞的增殖、侵袭和迁移能力增加。相反，PARP 6表达水平的升高具有相反的效果。通过基因芯片分析结合实验验证，我们证实PARP 6可以通过诱导降解抑制XRCC 6的表达，从而影响Wnt/β-Catenin信号通路，从而有助于肝癌的抑制。进一步的机制研究表明，泛素连接酶HDM 2可以与PARP 6和XRCC 6相互作用，并介导PARP 6对XRCC 6降解的调节作用。总而言之，PARP 6似乎通过XRCC 6/Wnt/β-连环蛋白信号轴抑制HCC进展，并可用作临床监测HCC发展的生物标志物。
PARP6 belongs to the mono-ADP-ribosyltransferase family and has been shown to be involved in the genesis and development of some tumours. However, the role of PARP6 in hepatocellular carcinoma (HCC) development remains to be fully elucidated. In the current study, we demonstrated that PARP6 was expressed at a low level in HCC cells and was negatively related to the degree of tumour differentiation. Additionally, silencing PARP6 led to an increase in the proliferation, invasion and migration ability of HCC cells in both in vitro and in vivo assays. Conversely, an elevation in the PARP6 expression level had the opposite effect. Through gene chip analysis combined with experimental verification, we confirmed that PARP6 can inhibit the expression of XRCC6 by inducing degradation and thus affect the Wnt/β-Catenin signalling pathway, which contributes to the suppression of HCC. Further mechanistic investigation demonstrated that the ubiquitin ligase HDM2 can interact with PARP6 and XRCC6, and mediated the regulatory effect of PARP6 on XRCC6 degradation. Taking together, PARP6 appears to inhibit HCC progression through the XRCC6/Wnt/β-catenin signal axis and could be used as a biomarker for the clinical monitoring of HCC development.
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影响因子：
9
作者：
Yang, Lian-Yue;Fang, Feng;Wu, Fan
通讯作者：
Wu, Fan
影响因子：
5.2
作者：
H. Tuncel;Shinji Tanaka;S. Oka;S. Nakai;Ryuichiro Fukutomi;Mayumi Okamoto;T. Ota;H. Kaneko;M. Tatsuka;F. Shimamoto
通讯作者：
H. Tuncel;Shinji Tanaka;S. Oka;S. Nakai;Ryuichiro Fukutomi;Mayumi Okamoto;T. Ota;H. Kaneko;M. Tatsuka;F. Shimamoto
影响因子：
11.8
作者：
Krishnamurthy N;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
3.7
作者：
O. Tavana;N. Puebla-Osorio;Jiseong Kim;M. Sang;S. Jang;Chengming Zhu
通讯作者：
O. Tavana;N. Puebla-Osorio;Jiseong Kim;M. Sang;S. Jang;Chengming Zhu
影响因子：
11.2
作者：
Wang, Zebin;Grosskurth, Shaun E.;Chen, Huawei
通讯作者：
Chen, Huawei