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本文引用的文献

1
MiR-421 inhibits the malignant phenotype in glioma by directly targeting MEF2D.微小RNA-421通过直接靶向心肌增强因子2D抑制神经胶质瘤的恶性表型。
Am J Cancer Res. 2017 Apr 1;7(4):857-868. eCollection 2017.
2
MicroRNA-1468-5p inhibits glioma cell proliferation and induces cell cycle arrest by targeting RRM1.微小RNA-1468-5p通过靶向核糖核苷酸还原酶M1抑制胶质瘤细胞增殖并诱导细胞周期停滞。
Am J Cancer Res. 2017 Apr 1;7(4):784-800. eCollection 2017.
3
MicroRNA-520b Suppresses Proliferation, Migration, and Invasion of Spinal Osteosarcoma Cells via Downregulation of Frizzled-8.微小 RNA-520b 通过下调卷曲蛋白-8 抑制脊髓骨肉瘤细胞的增殖、迁移和侵袭。
Oncol Res. 2017 Sep 21;25(8):1297-1304. doi: 10.3727/096504017X14873430389189. Epub 2017 Feb 28.
4
MicroRNA-101 inhibits proliferation, migration and invasion in osteosarcoma cells by targeting ROCK1.微小RNA-101通过靶向ROCK1抑制骨肉瘤细胞的增殖、迁移和侵袭。
Am J Cancer Res. 2017 Jan 1;7(1):88-97. eCollection 2017.
5
MiR-520b/e Regulates Proliferation and Migration by Simultaneously Targeting EGFR in Gastric Cancer.微小RNA-520b/e通过同时靶向表皮生长因子受体调控胃癌的增殖与迁移
Cell Physiol Biochem. 2016;40(6):1303-1315. doi: 10.1159/000453183. Epub 2016 Dec 19.
6
PPARα, a predictor of patient survival in glioma, inhibits cell growth through the E2F1/miR-19a feedback loop.PPARα是神经胶质瘤患者生存的一个预测指标,它通过E2F1/miR-19a反馈环抑制细胞生长。
Oncotarget. 2016 Dec 20;7(51):84623-84633. doi: 10.18632/oncotarget.13170.
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Glucose transport: meeting the metabolic demands of cancer, and applications in glioblastoma treatment.葡萄糖转运:满足癌症的代谢需求及其在胶质母细胞瘤治疗中的应用
Am J Cancer Res. 2016 Aug 1;6(8):1599-608. eCollection 2016.
8
Methyl-CpG-binding protein MBD2 plays a key role in maintenance and spread of DNA methylation at CpG islands and shores in cancer.甲基化CpG结合蛋白MBD2在癌症中CpG岛和海岸区域DNA甲基化的维持与扩散过程中发挥关键作用。
Oncogene. 2017 Mar;36(10):1328-1338. doi: 10.1038/onc.2016.297. Epub 2016 Sep 5.
9
Downregulation of miR-221 Inhibits Cell Migration and Invasion through Targeting Methyl-CpG Binding Domain Protein 2 in Human Oral Squamous Cell Carcinoma Cells.miR-221的下调通过靶向人口腔鳞状细胞癌细胞中的甲基化CpG结合域蛋白2抑制细胞迁移和侵袭。
Biomed Res Int. 2015;2015:751672. doi: 10.1155/2015/751672. Epub 2015 Dec 16.
10
Neuropilin-1 (NRP-1) and Magnetic Nanoparticles, a Potential Combination for Diagnosis and Therapy of Gliomas.神经纤毛蛋白-1(NRP-1)与磁性纳米颗粒:一种用于神经胶质瘤诊断与治疗的潜在组合
Curr Pharm Des. 2015;21(37):5434-49. doi: 10.2174/1381612821666150917092658.

微小RNA-520b通过直接靶向甲基化结合结构域蛋白2抑制神经胶质瘤的发展。

MiR-520b inhibits the development of glioma by directly targeting MBD2.

作者信息

Cui Sitong, Liu Liang, Wan Teng, Jiang Lei, Shi Yan, Luo Liangsheng

机构信息

Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical UniversityNanjing 210006, Jiangsu, China.

Department of Cardiology, Jiangsu Province Official HospitalNanjing 210024, Jiangsu, China.

出版信息

Am J Cancer Res. 2017 Jul 1;7(7):1528-1539. eCollection 2017.

PMID:28744402
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5523033/
Abstract

MicroRNAs play important roles in the process of cancer, which microRNA-520b (miR-520b) has been reported to play critical roles in tumor progression in many types of cancers. However, its role in glioma remains unknown. In this study, we found that miR-520b could inhibit growth and progression in glioma by targeting methyl-CpG-binding domain 2 (MBD2). First, we analyzed the expression of miR-520b in different glioma grades and different cell lines (U87, U251 and astrocyte). Then we assessed the effect of miR-520b on glucose metabolism, invasion, angiogenesis and chemosensitivity in U87 and U251 cells. By using an online database, miR-520b was found to directly bind to the 3'-untranslated regions (3'-UTR) of MBD2 and reduce its expression at the protein level, which further inhibits the development of glioma. MBD2 was also found to be over-expressed in human glioma tissues and in U87 and U251 cells and its level was inversely correlated with that of miR-520b. Furthermore, restoration of MBD2 partially rescued the miR-520b-induced inhibitory effect on glucose metabolism, invasion, angiogenesis and chemosensitivity in glioma cells. In summary, to date, this is the first study to demonstrate that miR-520b functions as a tumor suppressor in glioma by directly targeting MBD2, suggesting that MBD2 may be a potential therapeutic target for glioma.

摘要

微小RNA在癌症发生过程中发挥着重要作用,据报道,微小RNA-520b(miR-520b)在多种癌症的肿瘤进展中起关键作用。然而,其在胶质瘤中的作用尚不清楚。在本研究中,我们发现miR-520b可通过靶向甲基化CpG结合结构域2(MBD2)抑制胶质瘤的生长和进展。首先,我们分析了miR-520b在不同胶质瘤分级和不同细胞系(U87、U251和星形胶质细胞)中的表达。然后,我们评估了miR-520b对U87和U251细胞葡萄糖代谢、侵袭、血管生成和化学敏感性的影响。通过使用在线数据库,发现miR-520b直接与MBD2的3'-非翻译区(3'-UTR)结合,并在蛋白质水平降低其表达,从而进一步抑制胶质瘤的发展。还发现MBD2在人胶质瘤组织以及U87和U251细胞中过表达,其水平与miR-520b呈负相关。此外,恢复MBD2部分挽救了miR-520b诱导的对胶质瘤细胞葡萄糖代谢、侵袭、血管生成和化学敏感性的抑制作用。总之,迄今为止,这是第一项证明miR-520b通过直接靶向MBD2在胶质瘤中发挥肿瘤抑制作用的研究,表明MBD2可能是胶质瘤的潜在治疗靶点。