Repression of Dok7 expression mediated by DNMT1 promotes glioma cells proliferation - 25/08/18

Doi : 10.1016/j.biopha.2018.06.156

Cheng-Dao Hua ^a,^b,^{^{1
This author contributes equally to the first author.}}, Er-Bao Bian ^a,^b,^{^{1
This author contributes equally to the first author.}}, Er-Feng Chen ^a,^b, Zhi-Hao Yang ^a,^b, Feng Tang ^a,^b, Hong-Liang Wang ^a,^b, Bing Zhao ^a,^b,^⁎
^a Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
^b Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, 230601, China

^⁎Corresponding author at: Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Cerebral Vascular Disease Research Center, Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China.Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Cerebral Vascular Disease Research Center, Anhui Medical University, 678 Fu Rong RoadHefeiAnhui ProvinceChina

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Abstract

Malignant glioma is one of the most common primary human tumors in the central nervous system. The molecular mechanisms of the progression and development of glioma have been largely unexplored. In this study, we illustrated that the expression of Dok7 was downregulation in human glioma tissues. Dok7 overexpression significantly inhibits proliferation and colony formation in vitro, and the xenograft tumor formation in vivo. In addition, 5-Aza-2′-deoxycytidine (5-Aza), a DNA methylation inhibitor, preventing the loss of Dok7 expression by decreasing aberrant hypermethylation of Dok7 promoter in glioma cells. More importantly, DNMT1 knockdown induced the demethylation of Dok7 promoter, and enhanced the expression of Dok7 in gliomas. These results suggest that epigenetic silencing of Dok7 may provide a novel glioma treatment strategy.

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Keywords : Glioma, Dok7, 5-Aza, DNMT1

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Vol 106

P. 678-685 - octobre 2018 Retour au numéro

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Repression of Dok7 expression mediated by DNMT1 promotes glioma cells proliferation - 25/08/18

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