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cIAP2 通过 NF-κB 信号通路影响肝癌细胞的增殖和侵袭。

cIAP2 via NF-κB signalling affects cell proliferation and invasion in hepatocellular carcinoma.

机构信息

Department of Hepatobiliary Surgery, Affiliated Putian Hospital of Putian College, 363100, Fujian, China.

Department of Pathology, Affiliated Putian Hospital of Putian College, 363100, Fujian, China.

出版信息

Life Sci. 2021 Feb 1;266:118867. doi: 10.1016/j.lfs.2020.118867. Epub 2020 Dec 10.

DOI:10.1016/j.lfs.2020.118867
PMID:33310033
Abstract

AIMS

To investigate the role of cIAP2 in the malignant biological behaviours of hepatocellular carcinoma (HCC) cells and determine its mechanism of action.

MAIN METHODS

cIAP2 protein expression was detected via immunohistochemistry (IHC) in 102 HCC specimens and 43 paracancerous liver tissues, and its relationship with clinicopathological features and patient prognosis was analysed. Then, short interfering RNA (siRNA) technology was used to knock down cIAP2 expression in BEL7402 and HepG2 cells. Cell Counting Kit-8 (CCK8) and Transwell assays were used to determine cell proliferation and invasion after knockdown of cIAP2 expression. The relationship between cIAP2 and the NF-κB pathway was explored via western blotting (WB) and a dual luciferase reporter system. Finally, nude mouse models of liver cancer were established to detect the effect of cIAP2 on tumourigenicity and the proliferation activity of orthotopic HCC cells.

KEY FINDINGS

cIAP2 expression was significantly increased in HCC tissues and was correlated with intravascular thrombosis in HCC. High cIAP2 expression was correlated with poor patient prognosis. cIAP2 knockdown significantly reduced the proliferation and invasion of BEL7402 and HepG2 cells and the activity of the NF-κB pathway. Animal experiments showed that cIAP2 knockdown reduced the tumourigenicity of HepG2 cells in the liver of nude mice and the proliferation activity of the orthotopic HCC cells.

SIGNIFICANCE

cIAP2 plays an important role in HCC proliferation and invasion and may exert its effects via the NF-κB signalling pathway.

摘要

目的

研究 cIAP2 在肝癌(HCC)细胞恶性生物学行为中的作用,并确定其作用机制。

主要方法

采用免疫组织化学(IHC)检测 102 例 HCC 标本和 43 例癌旁肝组织中 cIAP2 蛋白的表达情况,分析其与临床病理特征和患者预后的关系。然后,采用短发夹 RNA(siRNA)技术敲低 BEL7402 和 HepG2 细胞中的 cIAP2 表达。细胞计数试剂盒(CCK8)和 Transwell 实验用于检测敲低 cIAP2 表达后细胞增殖和侵袭能力的变化。通过 Western blot(WB)和双荧光素酶报告系统探索 cIAP2 与 NF-κB 通路的关系。最后,建立裸鼠肝癌模型,检测 cIAP2 对肿瘤发生和原位 HCC 细胞增殖活性的影响。

主要发现

cIAP2 在 HCC 组织中的表达明显增加,与 HCC 中的血管内血栓形成有关。cIAP2 高表达与患者预后不良相关。cIAP2 敲低显著降低了 BEL7402 和 HepG2 细胞的增殖和侵袭能力,以及 NF-κB 通路的活性。动物实验表明,cIAP2 敲低降低了 HepG2 细胞在裸鼠肝脏中的致瘤性和原位 HCC 细胞的增殖活性。

意义

cIAP2 在 HCC 的增殖和侵袭中发挥重要作用,可能通过 NF-κB 信号通路发挥作用。

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