DEC1 is required for anti-apoptotic activity of gastric cancer cells under hypoxia by promoting Survivin expression
DEC1 is required for anti-apoptotic activity of gastric cancer cells under hypoxia by promoting Survivin expression
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DEC1是缺氧条件下胃癌细胞通过促进Survivin表达而发挥抗凋亡活性所必需的
DOI：
10.1007/s10120-017-0780-z
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发表时间：
2018-07-01
期刊：
影响因子：
7.4
通讯作者：
Ma, Xiaoli
中科院分区：
文献类型：
--
作者：
Jia, Yanfei;Hu, Rui;Ma, Xiaoli
背景人类分化胚胎软骨细胞表达基因1(DEC1)已被报道在多种类型的肿瘤中过表达，并通过参与多种生物学过程与肿瘤的发生有关。然而，DEC1在癌变过程中的复杂机制仍存在争议，其在胃癌发生发展和恶变中的作用尚不清楚。SRNA慢病毒感染可下调GC细胞中DEC1的水平。我们还评估了DEC1下调对异种移植瘤体内生长的影响。用CCK8比色法和流式细胞仪检测细胞存活率和凋亡率。Western blotting检测DEC1、Survivin和Bcl2的表达。用荧光素酶报告基因验证DEC1的下游靶点。结果DEC1基因的表达下调可抑制GC细胞的体外增殖和体内致瘤性。我们观察到，低氧诱导的DEC1的表达通过上调Survivin的转录水平来保护GC细胞免受凋亡。此外，胃癌组织切片中DEC1与Survivin表达呈正相关。DEC1和Survivin高表达的胃癌患者预后不良。结论DEC1通过促进Survivin的表达，在低氧条件下发挥抗胃癌细胞的抗凋亡调节作用。我们的研究证明了DEC1在肿瘤发生中的关键作用，并强调了DEC1在胃癌细胞凋亡调控中的新作用。
BackgroundHuman 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.MethodsWe 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.ResultsDownregulation 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.ConclusionsDEC1 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.