DEC1 is required for anti-apoptotic activity of gastric cancer cells under hypoxia by promoting Survivin expression
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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.
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.
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.
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.
KeywordsDEC1 Gastric cancer Anti-apoptosis Hypoxia Survivin
This work was financially supported by the National Natural Science Foundation of China (Nos. 31671468 and 81602593), the Chinese Postdoctoral Science Foundation (No. 2016M602152), the Shandong Provincial Natural Science Foundation of China (Nos. 2016ZRA01062, ZR2015HM018 and ZR2012HM061), and the Jinan Postdoctoral Innovation Project (172634).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent statement
All study participants, or their legal guardian, provided informed written consent before study enrollment. The Ethics Committee of Jinan Cental Hospital approved this study.
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