期刊
ONCOTARGET
卷 7, 期 26, 页码 40266-40284出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9733
关键词
JARID2; hepatocellular carcinoma; invasion; metastasis; epithelial-mesenchymal transition
资金
- Clinical Subjects' Key Project of Ministry of Health
- National Science and Technology Major Projects [2012ZX10002012-011]
- National Natural Science Foundation of China [81172018, 81272395, 81330057]
- National Keystone Basic Research Program of China [2009CB51800]
- Fundamental Research Funds for the Central Universities of Central South University [2013zzts098]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20130162130007]
JARID2 is crucial for maintenance of pluripotency and differentiation of embryonic stem cells. However, little is known about the role of JARID2 in metastasis of hepatocellular carcinoma (HCC). This study found that JARID2 expression was significantly higher in HCC tissues than that in adjacent non-tumor liver tissues (ANLTs), and its expression level correlated with HCC metastasis. High JARID2 expression was significantly correlated with multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P < 0.05) and indicated poor prognosis of HCC in training and validation cohorts (all P < 0.05) totaling 182 patients. High JARID2 expression was an independent and significant risk factor for disease-free survival (DFS; P = 0.017) and overall survival (OS; P = 0.041) after curative liver resection in training cohort, and also validated as an independent and significant risk factor for DFS (P = 0.033) and OS (P = 0.031) in validation cohort. Moreover, down-regulation of JARID2 dramatically inhibited HCC cell migration, invasion, proliferation in vitro and metastasis in vivo, whereas overexpression of JARID2 significantly increased migration, invasion, proliferation in vitro and metastasis in vivo. Mechanistically, the data showed that JARID2 exerted its function by repressing PTEN expression through increasing H3K27 trimethylation (H3K27me3) at PTEN promoter region, which subsequently resulted in activation of protein kinase B (AKT) and enhanced epithelial-mesenchymal transition (EMT). In conclusion, this study revealed that JARID2 promotes invasion and metastasis of HCC by facilitating EMT through PTEN/AKT signaling.
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