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CBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma

文献类型：期刊论文

作者Tang, Bo2; Tian, Yu1,3; Liao, Yong2; Li, Zeming2; Yu, Shuiping2; Su, Huizhao2; Zhong, Fudi2; Yuan, Guandou2; Wang, Yan2; Yu, Hongping2
刊名CELL DEATH & DISEASE
出版日期2019-01-18
卷号10页码:14
ISSN号2041-4889
DOI10.1038/s41419-018-1288-0
通讯作者Qiu, Xiaoqiang(Dr_qiuxiaoqiang@163.com) ; He, Songqing(drhesongqing@126.com)
英文摘要Polycomb group family is a class of proteins that have important roles in both physiological and pathological processes, and its family member Chromobox homolog 8 (CBX8) regulates cell differentiation, aging, and cell cycle progression in numerous carcinomas; however, the effects and underlying mechanisms of CBX8 in hepatocellular carcinoma (HCC) are rarely reported. We found that CBX8 expression in clinical HCC specimens correlates inversely with patient survival. In HCC cells, we found that enforced overexpression of CBX8 induces epithelial-mesenchymal transition, invasive migration, and stem cell-like traits, which are associated with increased tumor growth and metastasis in mice. Conversely, CBX8 silencing inhibits the aggressive phenotype of HCC cells that have high CBX8 expression. Mechanistically, CBX8 modulates H3K27me3 in the gene promoter of bone morphogenetic protein 4 (BMP4), which is associated with active BMP4 transcription and, consequently, the activation of Smads and mitogen-activated protein kinases. BMP4 expression reverses the effects of CBX8 silencing in inhibiting epithelial-mesenchymal transition, stemness, and metastasis. Our results establish CBX8 as a critical driver of HCC stem cell-like and metastatic behaviors and characterize its role in modulating BMP4 expression. These findings have implications for the targeting of CBX8 as an approach to HCC prognosis and treatment.
WOS关键词EPITHELIAL-MESENCHYMAL TRANSITION ; BONE MORPHOGENETIC PROTEIN ; POLYCOMB GROUP PROTEIN ; CANCER ; PROLIFERATION ; METHYLATION ; METASTASIS ; SENESCENCE ; INVASION ; CELLS
资助项目National Natural Science Foundation of China[81430014] ; National Natural Science Foundation of China[81360367] ; National Natural Science Foundation of China[81560393] ; Guangxi Science Fund for Distinguished Young Scholars Program[2016GXNSFFA380003] ; Natural Science Foundation of Guangxi[2015GXNSFDA139026] ; Scientific Research and Technology Development Project for Guilin[20140310-2-2] ; Scientific Research and Technology Development Project for Guilin[20150133-6] ; 111 Project[D17011] ; Guangxi Health and Family Planning Commission 139 Leading Talents Training Plan ; 2017 Talent Construction Project of Guilin
WOS研究方向Cell Biology
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000472753500004
资助机构National Natural Science Foundation of China ; National Natural Science Foundation of China ; Guangxi Science Fund for Distinguished Young Scholars Program ; Guangxi Science Fund for Distinguished Young Scholars Program ; Natural Science Foundation of Guangxi ; Natural Science Foundation of Guangxi ; Scientific Research and Technology Development Project for Guilin ; Scientific Research and Technology Development Project for Guilin ; 111 Project ; 111 Project ; Guangxi Health and Family Planning Commission 139 Leading Talents Training Plan ; Guangxi Health and Family Planning Commission 139 Leading Talents Training Plan ; 2017 Talent Construction Project of Guilin ; 2017 Talent Construction Project of Guilin ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Guangxi Science Fund for Distinguished Young Scholars Program ; Guangxi Science Fund for Distinguished Young Scholars Program ; Natural Science Foundation of Guangxi ; Natural Science Foundation of Guangxi ; Scientific Research and Technology Development Project for Guilin ; Scientific Research and Technology Development Project for Guilin ; 111 Project ; 111 Project ; Guangxi Health and Family Planning Commission 139 Leading Talents Training Plan ; Guangxi Health and Family Planning Commission 139 Leading Talents Training Plan ; 2017 Talent Construction Project of Guilin ; 2017 Talent Construction Project of Guilin ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Guangxi Science Fund for Distinguished Young Scholars Program ; Guangxi Science Fund for Distinguished Young Scholars Program ; Natural Science Foundation of Guangxi ; Natural Science Foundation of Guangxi ; Scientific Research and Technology Development Project for Guilin ; Scientific Research and Technology Development Project for Guilin ; 111 Project ; 111 Project ; Guangxi Health and Family Planning Commission 139 Leading Talents Training Plan ; Guangxi Health and Family Planning Commission 139 Leading Talents Training Plan ; 2017 Talent Construction Project of Guilin ; 2017 Talent Construction Project of Guilin ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Guangxi Science Fund for Distinguished Young Scholars Program ; Guangxi Science Fund for Distinguished Young Scholars Program ; Natural Science Foundation of Guangxi ; Natural Science Foundation of Guangxi ; Scientific Research and Technology Development Project for Guilin ; Scientific Research and Technology Development Project for Guilin ; 111 Project ; 111 Project ; Guangxi Health and Family Planning Commission 139 Leading Talents Training Plan ; Guangxi Health and Family Planning Commission 139 Leading Talents Training Plan ; 2017 Talent Construction Project of Guilin ; 2017 Talent Construction Project of Guilin
源URL[http://cas-ir.dicp.ac.cn/handle/321008/176037]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Qiu, Xiaoqiang; He, Songqing
作者单位1.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China
2.Guangxi Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Nanning, Guangxi, Peoples R China
3.Dalian Med Univ, Hosp 2, Dept Vasc Surg, Dalian, Liaoning, Peoples R China
4.Med Univ South Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA
5.Guangxi Med Univ, Sch Publ Hlth, Nanning, Guangxi, Peoples R China
推荐引用方式
GB/T 7714		 Tang, Bo,Tian, Yu,Liao, Yong,et al. CBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma[J]. CELL DEATH & DISEASE,2019,10:14.
APA Tang, Bo.,Tian, Yu.,Liao, Yong.,Li, Zeming.,Yu, Shuiping.,...&He, Songqing.(2019).CBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma.CELL DEATH & DISEASE,10,14.
MLA Tang, Bo,et al."CBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma".CELL DEATH & DISEASE 10(2019):14.

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来源：大连化学物理研究所

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