Inflammation-Induced Long Intergenic Noncoding RNA (LINC00665) Increases Malignancy Through Activating the Double-Stranded RNA-Activated Protein Kinase/Nuclear Factor Kappa B Pathway in Hepatocellular Carcinoma
Inflammation-Induced Long Intergenic Noncoding RNA (LINC00665) Increases Malignancy Through Activating the Double-Stranded RNA-Activated Protein Kinase/Nuclear Factor Kappa B Pathway in Hepatocellular Carcinoma
复制标题
炎症诱导的长基因间非编码 RNA (LINC00665) 通过激活双链 RNA 激活蛋白激酶/核因子 Kappa B 通路增加肝细胞癌的恶性程度
DOI：
10.1002/hep.31195
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发表时间：
2020-10-19
期刊：
影响因子：
13.5
通讯作者：
He, Xianghuo
中科院分区：
文献类型：
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作者：
Ding, Jie;Zhao, Jingjing;He, Xianghuo
背景与目的核因子-κ B（NF-κ B B）信号通路在炎症和肿瘤发生中起重要作用。在此，我们描述了肝细胞癌（HCC）中NF-κ B信号激活诱导的长基因间非编码（LINC）RNA，LINC 00665，其有助于增强HCC细胞的体外和体内细胞增殖。方法和结果LINC 00665与双链RNA（dsRNA）激活的蛋白激酶（PKR）发生物理相互作用，通过阻断泛素/蛋白酶体依赖性降解，增强PKR的激活，维持PKR蛋白的稳定性，从而对HCC细胞中NF-κ B信号传导产生正反馈调节。值得注意的是，HCC和LINC 00665较高的患者在临床上的结果较差。结论LINC 00665参与了肝癌细胞NF-κ B信号通路的激活，炎症性LINC 00665/PKR/NF-κ B环在肝癌的发生发展中起重要的致癌作用，可能成为潜在的治疗靶点。
Background and Aims The nuclear factor kappa B (NF-kappa B) signaling pathway is important for linking inflammation and tumorigenesis. Here, we characterized an NF-kappa B signaling activation-induced long intergenic noncoding (LINC) RNA in hepatocellular carcinoma (HCC), LINC00665, that contributes to the enhanced cell proliferation of HCC cells bothin vitroandin vivo. Approach and Results LINC00665 physically interacts with the double-stranded RNA (dsRNA)-activated protein kinase (PKR), enhances its activation, and maintains its protein stability by blocking ubiquitin/proteasome-dependent degradation, resulting in a positive feedback regulation of NF-kappa B signaling in HCC cells. Notably, patients with HCC and higher LINC00665 have poorer outcomes in the clinic. Conclusions Our findings indicate that LINC00665 is involved in the NF-kappa B signaling activation in HCC cells and that the inflammatory LINC00665/PKR/NF-kappa B loop plays important oncogenic roles in hepatic cancer progression and may be a potential therapeutic target.