Hypomethylation of CNTFR alpha is associated with proliferation and poor prognosis in lower grade gliomas
文献类型：期刊论文
| 作者 | Fan, Kun2,3; Li, Chunjie2,3; Ye, Dan2; Wang, Xiaowen3; Zhang, Haibo3; Hua, Wei3; Wang, Xiaowen4; Ramos, Romela Irene4; Marzese, Diego M.4; Hoon, Dave S. B.4 |
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2017 |
| 卷号 | 7期号:-页码:7079 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/s41598-017-07124-9 |
| 文献子类 | Article |
| 英文摘要 | Ciliary neurotrophic factor receptor a subunit (CNTFR alpha) and CNTF play important roles in neuron survival, glial differentiation and brain tumor growth. However, the molecular mechanisms of CNTFR alpha regulation and its clinical significance in glioma remain largely unknown. Here, we found CNTFR alpha was overexpressed in lower grade gliomas (LGG) compared with glioblastoma (GBM) and normal brain specimens in TCGA datasets and in an independent cohort. Bioinformatics analysis revealed a CpG shore of the CNTFR alpha gene regulated its mRNA expression in TCGA datasets. This observation was further validated with clinical specimens and functionally verified using demethylating agents. Additionally, we observed that independent of IDH mutation status, methylation of CNTFR alpha was significantly correlated with down-regulated CNTFR alpha gene expression and longer LGG patient survival. Interestingly, combination of CNTFR alpha methylation and IDH mutation significantly (p < 0.05) improved the prognostic prediction in LGG patients. Furthermore, the role of CNTFR alpha in glioma proliferation and apoptosis through the PI3K/AKT pathways was demonstrated by supplementation with exogenous CNTF in vitro and siRNA knockdown in vivo. Our study demonstrated that hypomethylation leading to CNTFR alpha up-regulation, together with autocrine expression of CNTF, was involved in glioma growth regulation. Importantly, DNA methylation of CNTFR alpha might serve as a potential epigenetic theranostic target for LGG patients. |
| 学科主题 | Science & Technology - Other Topics |
| WOS关键词 | CILIARY NEUROTROPHIC FACTOR ; CELL LUNG-CANCER ; SIGNALING PATHWAYS ; DNA METHYLATION ; GLIOBLASTOMA ; DIFFERENTIATION ; CONNEXIN43 ; CYTOKINE ; SURVIVAL ; NEURONS |
| 语种 | 英语 |
| WOS记录号 | WOS:000406764200111 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1053]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Providence St John Hlth Ctr, Sequencing Ctr, John Wayne Canc Inst JWCI, Santa Monica, CA USA, 2.Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Shanghai, Peoples R China; 3.Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai, Peoples R China; 4.Providence St John Hlth Ctr, John Wayne Canc Inst JWCI, Dept Translat Mol Med, Santa Monica, CA USA; 5.Hebei Gen Hosp, Dept Ultrasound Diag, Shijiazhuang, Hebei, Peoples R China; 6.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Fan, Kun,Li, Chunjie,Ye, Dan,et al. Hypomethylation of CNTFR alpha is associated with proliferation and poor prognosis in lower grade gliomas[J]. SCIENTIFIC REPORTS,2017,7(-):7079. |
| APA | Fan, Kun.,Li, Chunjie.,Ye, Dan.,Wang, Xiaowen.,Zhang, Haibo.,...&,.(2017).Hypomethylation of CNTFR alpha is associated with proliferation and poor prognosis in lower grade gliomas.SCIENTIFIC REPORTS,7(-),7079. |
| MLA | Fan, Kun,et al."Hypomethylation of CNTFR alpha is associated with proliferation and poor prognosis in lower grade gliomas".SCIENTIFIC REPORTS 7.-(2017):7079. |
入库方式： OAI收割
来源：上海营养与健康研究所
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