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Journal of Molecular Signaling Updates

Journal of Molecular Signaling Updates - Volume 1

MicroRNA-129 Suppresses Glioblastoma Cell Proliferation by Targeting CDK6

Published on: 07 March 2016

Pages: 24-32

Dandan He,1,2Xiaoyan Chen,1,2 Peter S. Reinach,1,2 Jiao Wang,1,2Zhi-Qiang Ling,3 andDongsheng Yan1,2

1School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; 2Key Laboratory of Vision Science, Ministry of Health of the People's Republic of China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China and 3Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China

Abstract: MicroRNAs (miRNAs) are an endogenous class of non-coding RNAs approximately 22 nucleotides in length inhibiting gene function by directly binding to target mRNAs and either blocking translation or degrading the mRNAs. MicroRNA-129 (miR-129), an abundant miRNA in the central nervous system, has been linked to controlling tumor progression.Here, we characterized the role of miR-129 in controlling glioblastoma development. We demonstrated that miR-129 expression was downregulated in the T98G glioblastoma cell line and clinical specimens relative to normal brain tissue. On the other hand, DNA hypomethylating agents, 5-aza-2'-deoxycytidine and trichostatinAupregulatedmiR-129 expression. Transfection of miR-129 into T98G cells led to cell cycle G1 arrest and a significant decrease in cell growth. Using bioinformatics and luciferase gene reporter assay, we identified CDK6 as a gene target of miR-129. Downregulation of CDK6 protein expression by miR-129 was confirmed by subsequent Western blot analysis. Furthermore, CDK6 is upregulated in glioblastoma specimens. Finally, overexpression of miR-129 suppressed the growth of glioblastomain vivo. Our results further substantiate that miR-129 upregulation may be an effective approach to suppress glioblastoma development.

Keywords: miR-129, Proliferation, Gliolastoma, CDK6.

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