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【原创】Oncotarget:ISG15促进了肝细胞癌的发生和转移

已有 5944 次阅读 2016-8-29 17:41 |系统分类:论文交流

ISG15是一种泛素样分子,在I型干扰素刺激下能够显著地的上调。在本研究中,我们发现了ISG15在肝细胞癌(HCC)进程中的作用机制。结果表明,ISG15在HCC组织和多个细胞系中高表达,并与病理分期分级及预后密切相关。ISG15的表达不受HBV感染的影响。ISG15能够通过阻断XIAP对Survivin的降解,维持Survivin的稳定,提高了肝癌细胞的增殖和迁移能力。而敲低ISG15则抑制了肿瘤的生长,延长了肿瘤小鼠的寿命。所有的结果表明,ISG15高表达是HCC的一种固有特征,并且触发了肿瘤的发生和迁移。ISG15将会成为一种HCC预后监测的生物标志物,在ISG15过表达的患者中,ISG15可作为有效治疗HCC的靶点。

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2014 Sep 30;5(18):8429-41.

Interferon-stimulated gene 15 (ISG15) is a trigger for tumorigenesis and metastasis of hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with poor prognosis. IFN-stimulated genes 15 (ISG15) is an ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. However, the role of ISG15 in HCC remains unclear. In this study, we investigated the function of ISG15 during HCC progression and related mechanism using clinicopathological data, cell line and xenograft model. Our results indicated that ISG15 is highly expressed in HCC tissues and multiple HCC cell lines. ISG15 expression is significantly associated with the differentiation grade, metastatic of tumor and survival of HCC patients. However, the expression of ISG15 is not affected by HBV infection. ISG15 promotes the proliferation and migration of hepatocarcinoma cells through maintaining Survivin protein stabilization via sequestering XIAP from interacting with Survivin. Knowing down ISG15 with SiRNA inhibited the xenografted tumor growth and prolonged the lifespan of tumor-bearing mice. All these results support that ISG15 high expression is an intrinsic feature for HCC and a trigger for tumorigenesis and metastasis. ISG15 may be a prognostic biomarker and the inhibition of ISG15 could provide a therapeutic advantage for HCC patients over-expressing ISG15.





https://blog.sciencenet.cn/blog-3227923-999516.html

上一篇:【原创】J Exp Med:Mad2多聚谷氨酸化与巨核细胞的生成
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