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MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a

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Abstract

MicroRNAs are ∼21nt single-stranded RNAs and function as regulators of gene expression. Previous studies have shown that microRNAs play crucial roles in tumorigenesis by targeting the mRNAs of oncogenes or tumor suppressors. Here we show that brain-enriched miR-128 is down-regulated in glioma tissues and cell lines when compared to normal brain tissues. Overexpression of miR-128 in glioma cells inhibited cell proliferation. A bioinformatics search revealed a conserved target site within the 3′untranslated region (UTR) of E2F3a, a transcription factor that regulates cell cycle progression. The protein levels of E2F3a in gliomas and normal brain tissues were negatively correlated to the expression levels of miR-128 in these tissues. Overexpression of miR-128 suppressed a luciferase-reporter containing the E2F3a-3′UTR and reduced the level of E2F3a protein in T98G cells. Moreover, knocking down of E2F3a had similar effect as overexpression of miR-128, and overexpression of E2F3a can partly rescue the proliferation inhibition caused by miR-128. Taken together, our study demonstrates that miR-128 can inhibit proliferation of glioma cells through one of its targets, E2F3a.

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Acknowledgments

This work was supported by funds from the National Natural Sciences Foundation of China (nos. 30608022, 90612019, 30430200, 30721063), “863” project (nos. 2006AA0Z137, 2006AA02A304), “973” project (nos. 2004CB518604, 2005CB2507, 2006CB504100, 2007CB946902, 2007CB946900), Program for New Century Excellent Talents in University (no. NCET-07-0505).

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Authors and Affiliations

  1. The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China

    Yu Zhang, Tengfei Chao, Ran Li, Wei Liu, Yang Chen, Xingqi Yan, Yanhua Gong, Bin Yin, Boqing Qiang, Jiangang Yuan & Xiaozhong Peng

  2. Graduate School, Peking Union Medical College, Tsinghua University, Beijing, 100005, China

    Yu Zhang, Tengfei Chao, Ran Li, Wei Liu, Yang Chen & Xingqi Yan

  3. The Department of Neurosurgery, Beijing Tiantan Hospital, Beijing, 100050, China

    Wei Liu & Jizhong Zhao

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  1. Yu Zhang
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  2. Tengfei Chao
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  3. Ran Li
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  4. Wei Liu
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  5. Yang Chen
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  9. Wei Liu
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  10. Boqing Qiang
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  11. Jizhong Zhao
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  12. Jiangang Yuan
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  13. Xiaozhong Peng
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Correspondence to Jiangang Yuan or Xiaozhong Peng.

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Zhang, Y., Chao, T., Li, R. et al. MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a. J Mol Med 87, 43–51 (2009). https://doi.org/10.1007/s00109-008-0403-6

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  • DOI: https://doi.org/10.1007/s00109-008-0403-6

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