Yuan Wang, Bin Sun, Wei Wei, Tao Han, Jing Ma, Xiaodong Li, Chuanchun Han, Zhikun Lin
{"title":"NUCB2 通过激活 E2F4/PTGR1 轴促进肝癌细胞的生长和转移","authors":"Yuan Wang, Bin Sun, Wei Wei, Tao Han, Jing Ma, Xiaodong Li, Chuanchun Han, Zhikun Lin","doi":"10.7150/ijbs.97861","DOIUrl":null,"url":null,"abstract":"<b>Background:</b> 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./n<b>Methods:</b> 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 <i>in vivo</i> mouse xenograft model. Regulation of E2F4 by NUCB2 was identified by protein half-life and <i>in vivo</i> ubiquitylation assays. The relationship between E2F4 and prostaglandin reductase 1 (PTGR1) was investigated by qRT-PCR, RT-PCR, and chromatin immunoprecipitation assays./n<b>Results:</b> 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 <i>in vitro</i> and <i>in vivo</i>. 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./n<b>Conclusion:</b> 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\n","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"29 1","pages":""},"PeriodicalIF":8.2000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NUCB2 promotes hepatocellular carcinoma cell growth and metastasis by activating the E2F4/PTGR1 axis\",\"authors\":\"Yuan Wang, Bin Sun, Wei Wei, Tao Han, Jing Ma, Xiaodong Li, Chuanchun Han, Zhikun Lin\",\"doi\":\"10.7150/ijbs.97861\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<b>Background:</b> 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./n<b>Methods:</b> 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 <i>in vivo</i> mouse xenograft model. Regulation of E2F4 by NUCB2 was identified by protein half-life and <i>in vivo</i> ubiquitylation assays. The relationship between E2F4 and prostaglandin reductase 1 (PTGR1) was investigated by qRT-PCR, RT-PCR, and chromatin immunoprecipitation assays./n<b>Results:</b> 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 <i>in vitro</i> and <i>in vivo</i>. 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./n<b>Conclusion:</b> 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\\n\",\"PeriodicalId\":13762,\"journal\":{\"name\":\"International Journal of Biological Sciences\",\"volume\":\"29 1\",\"pages\":\"\"},\"PeriodicalIF\":8.2000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Biological Sciences\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.7150/ijbs.97861\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biological Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.7150/ijbs.97861","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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
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.