Valproic acid regulates the miR-155/Jarid2 axis by affecting miR-155 promoter methylation in glioma  

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作  者:Ruixuan Wang Yanhong Chen Weilu Kuang Wuzhong Jiang Wenjing Zeng Yinyun Chen Zhengzheng Liu 

机构地区:[1]Department of Oncology,Xiangya Hospital,Central South University,Changsha 410008,China [2]Department of Clinical Pharmacology,Xiangya Hospital,Central South University,Changsha 410008,China [3]The Third Department of Gastroenterology,Hunan Provincial People’s Hospital,Changsha 410000,China [4]National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha 410008,China

出  处:《Acta Biochimica et Biophysica Sinica》2024年第2期174-183,共10页生物化学与生物物理学报(英文版)

基  金:This work was supported by the grants from the National Natural Science Foundation of China(No.81803582)and the Hunan Provincial Natural Science Foundation of China(No.2020JJ4896).Conflict of interest。

摘  要:The most frequent primary brain tumor in adults is glioma,yet no effective curative treatments are currently available.Our previous study demonstrated the enhancing effects of JARID2 on glioma sensitivity to TMZ treat-ment.In this study,miR-155 is predicted to target JARID2.miR-155 is overexpressed in clinical glioma specimens and cell lines.miR-155 overexpression in glioma cells enhances cell viability and represses cell apoptosis.Through targeting,miR-155 inhibits JARID2 expression.miR-155 inhibition inhibits glioma cell viability and enhances cell apoptosis,whereas JARID2 knockdown enhances cell viability and inhibits cell apoptosis;JARID2 knockdown partially reverses miR-155 inhibition effects on glioma phenotypes.miR-155 inhibition reduces but knockdown of JARID2 promotes the tumor formation ability of glioma cells in vivo.Valproic acid(VPA)upregulates JARID2 expression,inhibits glioma cell viability and enhances cell apoptosis.VPA downregulates the expression level of miR-155 by increasing the methylation level of the miR-155 promoter,suggesting that the miR-155/JARID2 axis is implicated in VPA inhibition of glioma cell viability and enhancement of glioma cell apoptosis.This study de-monstrates a new mechanism of VPA treatment of gliomas by affecting the miR-155/JARID2 axis,which could be regarded as a new strategy for the prevention and treatment of glioma.

关 键 词:GLIOMAS MIR-155 JARID2 METHYLATION valproic acid 

分 类 号:R739.4[医药卫生—肿瘤]

 

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