Shuqiang Weng1,2, Harry L A Janssen3, Ningping Zhang1,2, Wenqing Tang1,2, Encheng Bai1,2, Biwei Yang4, Ling Dong5,6. 1. Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China. 2. Shanghai Institute of Liver Disease, Shanghai, People's Republic of China. 3. Toronto Center for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada. 4. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China. 5. Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China. dong.ling@zs-hospital.sh.cn. 6. Shanghai Institute of Liver Disease, Shanghai, People's Republic of China. dong.ling@zs-hospital.sh.cn.
Abstract
BACKGROUND: CAPS1 (calcium-dependent activator protein for secretion) is a multi-domain protein involved in regulating exocytosis of synaptic vesicles and dense-core vesicles. However, the expression and function of CAPS1 in cholangiocarcinoma (CCA) remains unclear. In the present study, we explored the role of CAPS1 in CCA carcinogenesis. METHODS: CAPS1 expression was explored using western blotting and immunohistochemistry in four CCA cell lines and clinical samples from 90 cases of CCA. The clinical significance of CAPS1 was analyzed. The biological function of CAPS1 in CCA cells was detected in vitro and in vivo. The underlying mechanism of CAPS1 function was explored by detecting the expression of critical molecules in its associated signaling pathways. The mechanism of CAPS1 downregulation in tumor tissues was explored using in silico prediction and luciferase reporter assays. RESULTS: CAPS1 expression was reduced in CCA cell lines and human tumor tissues. Loss of CAPS1 in tumor tissues was closely associated with poor prognosis of patients with CCA. Moreover, CAPS1 expression correlated significantly with tumor-node-metastasis stage, lymph node metastasis, and vascular invasion. Lentivirus-mediated CAPS1 overexpression substantially prevented clone formation, cell proliferation, and cell cycle progression. CAPS1 overexpression also suppressed carcinogenesis in nude mice. Mechanistically, CAPS1 overexpression greatly accelerated the ERK and p38 MAPK signal pathways. In addition, microRNA miR-30e-5p negatively regulated CAPS1 expression. CONCLUSION: These data showed that CAPS1 functions as a tumor suppressor in CCA. Reduced CAPS1 expression could indicate poor prognosis of patients with CCA.
BACKGROUND:CAPS1 (calcium-dependent activator protein for secretion) is a multi-domain protein involved in regulating exocytosis of synaptic vesicles and dense-core vesicles. However, the expression and function of CAPS1 in cholangiocarcinoma (CCA) remains unclear. In the present study, we explored the role of CAPS1 in CCA carcinogenesis. METHODS:CAPS1 expression was explored using western blotting and immunohistochemistry in four CCA cell lines and clinical samples from 90 cases of CCA. The clinical significance of CAPS1 was analyzed. The biological function of CAPS1 in CCA cells was detected in vitro and in vivo. The underlying mechanism of CAPS1 function was explored by detecting the expression of critical molecules in its associated signaling pathways. The mechanism of CAPS1 downregulation in tumor tissues was explored using in silico prediction and luciferase reporter assays. RESULTS:CAPS1 expression was reduced in CCA cell lines and humantumor tissues. Loss of CAPS1 in tumor tissues was closely associated with poor prognosis of patients with CCA. Moreover, CAPS1 expression correlated significantly with tumor-node-metastasis stage, lymph node metastasis, and vascular invasion. Lentivirus-mediated CAPS1 overexpression substantially prevented clone formation, cell proliferation, and cell cycle progression. CAPS1 overexpression also suppressed carcinogenesis in nude mice. Mechanistically, CAPS1 overexpression greatly accelerated the ERK and p38 MAPK signal pathways. In addition, microRNA miR-30e-5p negatively regulated CAPS1 expression. CONCLUSION: These data showed that CAPS1 functions as a tumor suppressor in CCA. Reduced CAPS1 expression could indicate poor prognosis of patients with CCA.
Authors: Jisce R Puik; Laura L Meijer; Tessa Ys Le Large; Mireia Mato Prado; Adam E Frampton; Geert Kazemier; Elisa Giovannetti Journal: Pharmacogenomics Date: 2017-08-23 Impact factor: 2.533
Authors: Suzanne Miller; Hazel A Rogers; Paul Lyon; Vikki Rand; Martyna Adamowicz-Brice; Steven C Clifford; James T Hayden; Sara Dyer; Stefan Pfister; Andrey Korshunov; Marie-Anne Brundler; James Lowe; Beth Coyle; Richard G Grundy Journal: Neuro Oncol Date: 2011-08 Impact factor: 12.300