NUCB2 通过激活 E2F4/PTGR1 轴促进肝癌细胞的生长和转移

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Biological Sciences Pub Date : 2024-09-03 DOI:10.7150/ijbs.97861
Yuan Wang, Bin Sun, Wei Wei, Tao Han, Jing Ma, Xiaodong Li, Chuanchun Han, Zhikun Lin
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引用次数: 0

摘要

背景:核结合蛋白 2(NUCB2)在各种癌症中的重要作用最近已得到认可。然而,它在肝细胞癌(HCC)中的生物学功能和调控机制仍不清楚:利用公共数据库、免疫组织化学和 Western 印迹法评估了 NUCB2 在 HCC 中的表达水平。使用集落形成、EdU、Transwell 试验和体内小鼠异种移植模型研究了 NUCB2 对细胞增殖和转移的影响。通过蛋白质半衰期和体内泛素化实验确定了 NUCB2 对 E2F4 的调控作用。通过qRT-PCR、RT-PCR和染色质免疫共沉淀实验研究了E2F4与前列腺素还原酶1(PTGR1)之间的关系:该研究发现,NUCB2在HCC组织中的表达明显高于正常肝组织,且高表达患者的存活率更短。抑制 NUCB2 可降低 HCC 细胞在体外和体内的增殖和转移潜能。抑制 NUCB2 可降低 PTGR1 的表达,从而减少细胞的增殖和迁移。我们的研究结果表明,NUCB2通过与E2F4相互作用来抑制E2F4的降解。此外,E2F4水平的增加通过直接与PTGR1启动子结合促进了PTGR1的转录:本研究证明了 NUCB2 在 HCC 中的致癌特性,并认为 NUCB2 通过激活 E2F4/PTGR1 轴促进了肝细胞癌的进展。
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NUCB2 promotes hepatocellular carcinoma cell growth and metastasis by activating the E2F4/PTGR1 axis
Background: The important role of nucleobindin 2 (NUCB2) in various cancers has been recently recognized. However, its biological functions and regulatory mechanisms in hepatocellular carcinoma (HCC) remain unclear./nMethods: The expression level of NUCB2 in HCC was assessed using public databases, immunohistochemistry, and Western blotting. The effects of NUCB2 on cell proliferation and metastasis were investigated using colony formation, EdU, Transwell assays, and an in vivo mouse xenograft model. Regulation of E2F4 by NUCB2 was identified by protein half-life and in vivo ubiquitylation assays. The relationship between E2F4 and prostaglandin reductase 1 (PTGR1) was investigated by qRT-PCR, RT-PCR, and chromatin immunoprecipitation assays./nResults: This study found that NUCB2 expression was significantly higher in HCC tissues than in normal liver tissues, and patients with high expression displayed shorter survival rates. Inhibition of NUCB2 reduced the proliferation and metastatic potential of HCC cells in vitro and in vivo. NUCB2 depletion reduced PTGR1 expression, which reduced cell proliferation and migration. Our findings suggested that NUCB2 suppressed E2F4 degradation by interacting with E2F4. Additionally, increased E2F4 levels facilitated PTGR1 transcription by directly binding to the PTGR1 promoter./nConclusion: This study demonstrated the oncogenic properties of NUCB2 in HCC and suggested that NUCB2 facilitates hepatocellular carcinoma progression by activating the E2F4/PTGR1 axis./n/n
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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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