CREBRF is a potent tumor suppressor of glioblastoma by blocking hypoxia-induced autophagy via the CREB3/ATG5 pathway
CREBRF is a potent tumor suppressor of glioblastoma by blocking hypoxia-induced autophagy via the CREB3/ATG5 pathway
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CREBRF 是一种有效的胶质母细胞瘤抑制剂，通过 CREB3/ATG5 途径阻断缺氧诱导的自噬
DOI：
10.3892/ijo.2016.3576
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发表时间：
2016-08-01
影响因子：
5.2
通讯作者：
Li, Gang
中科院分区：
文献类型：
--
作者：
Xue, Hao;Zhang, Jinsen;Li, Gang
缺氧诱导晚期胶质母细胞瘤细胞的保护性自噬，靶向这一过程可能改善胶质母细胞瘤患者的预后。最近的研究表明，胶质母细胞瘤细胞的自噬过程在广泛缺氧的情况下被上调。在这里，我们描述了胶质母细胞瘤细胞中的一种新的肿瘤抑制因子，其中缺氧下调了CREBRF的表达，并通过CREB3/ATG5途径作为胶质母细胞瘤细胞自噬的有效抑制剂。我们的研究结果表明，在不同级别的胶质瘤中，CREBRF表达与自噬和HIF-1 α水平呈负相关。考虑到CREBRF是CREB3的负调节因子，CREB3敲低也能抑制体外缺氧诱导的胶质母细胞瘤细胞自噬。总之，我们的研究结果为缺氧诱导胶质母细胞瘤细胞自噬的分子机制提供了新的见解，并表明缺氧/CREBRF/CREB3/ATG5通路在恶性胶质瘤的进展中起着核心作用。
Hypoxia induces protective autophagy in advanced glioblastoma cells, and targeting this process may improve the outcome for glioblastoma patients. Recent studies have suggested that the autophagic process is upregulated in glioblastoma cells in response to extensive hypoxia. Here, we describe a novel tumor suppressor in glioblastoma cells, whereby hypoxia downregulated CREBRF expression and acts as a potent inhibitor of autophagy in glioblastoma cells via the CREB3/ATG5 pathway. Our results demonstrate that CREBRF expression negatively correlates with autophagic and HIF-1 alpha levels in different grade gliomas. Given that CREBRF is a negative regulator of CREB3, CREB3 knockdown also repressed hypoxia-induced autophagy in glioblastoma cells in vitro. Collectively, our findings provide new insight into the molecular mechanisms underlying hypoxia-induced glioblastoma cell autophagy and indicate that the hypoxia/CREBRF/CREB3/ATG5 pathway plays a central role in malignant glioma progression.