Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment
| Autor: | Feng, Jianbo, Zhang, Yan, She, Xiaoling, Sun, Yingnan, Fan, Li, Ren, Xing, Fu, Haijuan, Liu, Changhong, Li, Peiyao, Zhao, Chunhua, Liu, Qiang, Liu, Qing, Li, Guiyuan, Wu, Minghua |
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| Rok vydání: | 2019 |
| Předmět: |
Clinical Sciences
Oncology and Carcinogenesis Apoptosis alpha Subunit Chromosomes Cell Line Mixed Function Oxygenases Genetic Autophagy Tumor Microenvironment Humans Oncology & Carcinogenesis Neoplastic Tumor Protein Stability Tumor Suppressor Proteins Pair 15 Intracellular Signaling Peptides and Proteins DNA Methylation Recombinant Proteins Neoplasm Proteins Up-Regulation Ankyrin Repeat Repressor Proteins Glucose Gene Expression Regulation Genes Von Hippel-Lindau Tumor Suppressor Protein Lactates Tumor Hypoxia Hypoxia-Inducible Factor 1 Glioblastoma Transcription Tumor Suppressor Human Half-Life |
| Zdroj: | Oncogene, vol 38, iss 1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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