Yan Liang1,2, Hesheng Luo1, Haidong Zhang2, Youhong Dong2, Ying Bao2. 1. 1 Department of Gastroenterology, Renmin Hospital of Wuhan University , Wuhan, China . 2. 2 Department of Oncology, Xiangyang No.1 People's Hospital, Hubei University of Medicine , XiangYang, Hubei, China .
Abstract
PURPOSE: To determine the expression and function of Delta/Notch-like EGF-related receptor (DNER) in hepatocellular carcinoma (HCC). METHODS: The expression of DNER in 84 HCC tissue samples and matched adjacent noncancerous specimens, as well as HCC cells, were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Survival analysis was evaluated using Kaplan-Meier method. For experiments in vitro, cell viability was measured by Cell Counting Kit-8 Assay and Colony Formation Assay. Furthermore, cell invasion and migration assays were performed with Transwell Assay. RESULTS: The results showed that DNER was overexpressed in the tissues and cell lines of HCC (all, p < 0.05), and the upregulated expression of DNER was significantly correlated with advanced pathologic stage (p = 0.013) and pathologic-M1 (p = 0.012) in HCC patients. Survival analysis revealed that patients with high DNER levels had worse overall survival (OS) than those with low DNER levels (p = 0.004). More importantly, DNER could be an independent predictor of prognosis for OS (HR = 2.582, 95% CI 1.239-5.380, p = 0.011). In vitro, knockdown of DNER significantly suppressed cell proliferation, colony formation, cell invasion, and cell migration in HepG2 cells. Moreover, inhibition of DNER inactivated PI3K/AKT signaling pathway by downregulating the expression of p-PI3K, p-AKT, and p-70s6k. CONCLUSIONS: Taken together, DNER could promote proliferation, migration, and invasion of HCC cells by regulating the activation of PI3K/AKT pathway, and it might act as a potential prognostic biomarker for HCC.
PURPOSE: To determine the expression and function of Delta/Notch-like EGF-related receptor (DNER) in hepatocellular carcinoma (HCC). METHODS: The expression of DNER in 84 HCC tissue samples and matched adjacent noncancerous specimens, as well as HCC cells, were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Survival analysis was evaluated using Kaplan-Meier method. For experiments in vitro, cell viability was measured by Cell Counting Kit-8 Assay and Colony Formation Assay. Furthermore, cell invasion and migration assays were performed with Transwell Assay. RESULTS: The results showed that DNER was overexpressed in the tissues and cell lines of HCC (all, p < 0.05), and the upregulated expression of DNER was significantly correlated with advanced pathologic stage (p = 0.013) and pathologic-M1 (p = 0.012) in HCC patients. Survival analysis revealed that patients with high DNER levels had worse overall survival (OS) than those with low DNER levels (p = 0.004). More importantly, DNER could be an independent predictor of prognosis for OS (HR = 2.582, 95% CI 1.239-5.380, p = 0.011). In vitro, knockdown of DNER significantly suppressed cell proliferation, colony formation, cell invasion, and cell migration in HepG2 cells. Moreover, inhibition of DNER inactivated PI3K/AKT signaling pathway by downregulating the expression of p-PI3K, p-AKT, and p-70s6k. CONCLUSIONS: Taken together, DNER could promote proliferation, migration, and invasion of HCC cells by regulating the activation of PI3K/AKT pathway, and it might act as a potential prognostic biomarker for HCC.
Authors: Peng Sun; Shuli Xia; Bachchu Lal; Charles G Eberhart; Alfredo Quinones-Hinojosa; Jarek Maciaczyk; William Matsui; Francesco Dimeco; Sara M Piccirillo; Angelo L Vescovi; John Laterra Journal: Stem Cells Date: 2009-07 Impact factor: 6.277
Authors: Lorna Richardson; Shanmugasundaram Venkataraman; Peter Stevenson; Yiya Yang; Julie Moss; Liz Graham; Nicholas Burton; Bill Hill; Jianguo Rao; Richard A Baldock; Chris Armit Journal: Nucleic Acids Res Date: 2013-11-21 Impact factor: 16.971