Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, 410013, Hunan, China.
The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410008, Hunan, China.
Oncogene. 2019 Jan;38(1):103-119. doi: 10.1038/s41388-018-0423-9. Epub 2018 Aug 6.
Ectopic epigenetic mechanisms play important roles in facilitating tumorigenesis. Here, we first demonstrated that ANKDD1A is a functional tumor suppressor gene, especially in the hypoxia microenvironment. ANKDD1A directly interacts with FIH1 and inhibits the transcriptional activity of HIF1α by upregulating FIH1. In addition, ANKDD1A decreases the half-life of HIF1α by upregulating FIH1, decreases glucose uptake and lactate production, inhibits glioblastoma multiforme (GBM) autophagy, and induces apoptosis in GBM cells under hypoxia. Moreover, ANKDD1A is highly frequently methylated in GBM. The tumor-specific methylation of ANKDD1A indicates that it could be used as a potential epigenetic biomarker as well as a possible therapeutic target.
异位表观遗传机制在促进肿瘤发生中起着重要作用。在这里，我们首先证明 ANKDD1A 是一种功能性肿瘤抑制基因，尤其是在缺氧微环境中。ANKDD1A 直接与 FIH1 相互作用，并通过上调 FIH1 抑制 HIF1α 的转录活性。此外，ANKDD1A 通过上调 FIH1 降低 HIF1α 的半衰期，减少葡萄糖摄取和乳酸生成，抑制胶质母细胞瘤（GBM）自噬，并在缺氧条件下诱导 GBM 细胞凋亡。此外，GBM 中 ANKDD1A 高度频繁甲基化。ANKDD1A 的肿瘤特异性甲基化表明它可以作为一种潜在的表观遗传生物标志物和可能的治疗靶点。
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