Yanfei Jia1, Rui Hu2, Ping Li3, Yan Zheng1, Yunshan Wang4,5, Xiaoli Ma6. 1. Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, People's Republic of China. 2. Department of Reproduction, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, People's Republic of China. 3. Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, People's Republic of China. 4. Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, People's Republic of China. sdjnwys@163.com. 5. Shandong Province Key Lab of Tumor Target Molecule, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, People's Republic of China. sdjnwys@163.com. 6. Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, People's Republic of China. mxl7125@126.com.
Abstract
BACKGROUND: Human differentiated embryonic chondrocyte-expressed gene 1 (DEC1), which has been reported to be overexpressed in several types of cancer, is associated with tumorigenesis through participation in several biological processes. However, the complex mechanisms underlying DEC1 during carcinogenesis are controversial, and its roles in the development and malignancy of gastric cancer (GC) remain unclear. METHODS: We measured DEC1 expression in human GC cell lines. DEC1 levels in GC cells were downregulated by shRNA lentivirus infection. We also evaluated the effect of DEC1 downregulation on xenograft growth in vivo. The viability and apoptosis of the cells were assayed using the CCK8 assay and flow cytometry. The levels of DEC1, Survivin, and Bcl-2 were evaluated by Western blotting. Luciferase reporter was used to verify the downstream target of DEC1. The association of DEC1 and Survivin expression with prognosis was investigated by immunohistochemistry. RESULTS: Downregulation of DEC1 inhibits GC cell proliferation in vitro and tumorigenicity in vivo. We observed that hypoxia-induced expression of DEC1 protects GC cells from apoptosis via transcriptional upregulation of Survivin. Furthermore, positive correlations between DEC1 with Survivin expression were observed in tissue sections from GC patients. Notably, GC patients with high expression levels of DEC1 and Survivin showed poor prognosis. CONCLUSIONS: DEC1 acts as an anti-apoptotic regulator in GC cells under hypoxia by promoting Survivin expression. Our study demonstrates the critical role of the DEC1 in oncogenesis and highlights a novel role for DEC1 in the regulation of cell apoptosis in GC.
BACKGROUND:Human differentiated embryonic chondrocyte-expressed gene 1 (DEC1), which has been reported to be overexpressed in several types of cancer, is associated with tumorigenesis through participation in several biological processes. However, the complex mechanisms underlying DEC1 during carcinogenesis are controversial, and its roles in the development and malignancy of gastric cancer (GC) remain unclear. METHODS: We measured DEC1 expression in human GC cell lines. DEC1 levels in GC cells were downregulated by shRNA lentivirus infection. We also evaluated the effect of DEC1 downregulation on xenograft growth in vivo. The viability and apoptosis of the cells were assayed using the CCK8 assay and flow cytometry. The levels of DEC1, Survivin, and Bcl-2 were evaluated by Western blotting. Luciferase reporter was used to verify the downstream target of DEC1. The association of DEC1 and Survivin expression with prognosis was investigated by immunohistochemistry. RESULTS: Downregulation of DEC1 inhibits GC cell proliferation in vitro and tumorigenicity in vivo. We observed that hypoxia-induced expression of DEC1 protects GC cells from apoptosis via transcriptional upregulation of Survivin. Furthermore, positive correlations between DEC1 with Survivin expression were observed in tissue sections from GC patients. Notably, GC patients with high expression levels of DEC1 and Survivin showed poor prognosis. CONCLUSIONS: DEC1 acts as an anti-apoptotic regulator in GC cells under hypoxia by promoting Survivin expression. Our study demonstrates the critical role of the DEC1 in oncogenesis and highlights a novel role for DEC1 in the regulation of cell apoptosis in GC.
Authors: Alexandra Giatromanolaki; Michael I Koukourakis; Efthimios Sivridis; Helen Turley; Charles C Wykoff; Kevin C Gatter; Adrian L Harris Journal: J Pathol Date: 2003-06 Impact factor: 7.996