MicroRNA-16 inhibits glioma cell growth and invasion through suppression of BCL2 and the nuclear factor-κB1/MMP9 signaling pathway

Authors

  • Tian-Quan Yang,

    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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    • These authors contributed equally to this work.
  • Xiao-Jun Lu,

    1. Department of Neurosurgery, The First People's Hospital of Tai Cang, Suzhou, China
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    • These authors contributed equally to this work.
  • Ting-Feng Wu,

    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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  • Da-Dong Ding,

    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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  • Zhao-Hui Zhao,

    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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  • Gui-Lin Chen,

    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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  • Xue-Shun Xie,

    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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  • Bin Li,

    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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  • Yong-Xin Wei,

    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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  • Ling-Chuan Guo,

    1. Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
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  • Yu Zhang,

    1. Department of Neurosurgery, The First People's Hospital of Tai Cang, Suzhou, China
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  • Yu-Lun Huang,

    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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  • You-Xin Zhou,

    Corresponding author
    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
    • You-Xin Zhou, Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu, 215006, China.

      Tel: +86-139-1552-2828; Fax: +86-512-6778-1170;

      E-mail: zhouyxyq2008@sohu.com

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  • Zi-Wei Du

    1. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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  • Funding Information

    Foundation of the Department of Health (K201106).

Abstract

Recent studies have identified a class of small non-coding RNA molecules, named microRNA (miRNA), that is dysregulated in malignant brain glioblastoma. Substantial data have indicated that miRNA-16 (miR-16) plays a significant role in tumors of various origins. This miRNA has been linked to various aspects of carcinogenesis, including cell apoptosis and migration. However, the molecular functions of miR-16 in gliomagenesis are largely unknown. We have shown that the expression of miR-16 in human brain glioma tissues was lower than in non-cancerous brain tissues, and that the expression of miR-16 decreased with increasing degrees of malignancy. Our data suggest that the expression of miR-16 and nuclear factor (NF)-κB1 was negatively correlated with glioma levels. MicroRNA-16 decreased glioma malignancy by downregulating NF-κB1 and MMP9, and led to suppressed invasiveness of human glioma cell lines SHG44, U87, and U373. Our results also indicated that upregulation of miR-16 promoted apoptosis by suppressing BCL2 expression. Finally, the upregulation of miR-16 in a nude mice model of human glioma resulted in significant suppression of glioma growth and invasiveness. Taken together, our experiments have validated the important role of miR-16 as a tumor suppressor gene in glioma growth and invasiveness, and revealed a novel mechanism of miR-16-mediated regulation in glioma growth and invasiveness through inhibition of BCL2 and the NF-κB1/MMP-9 signaling pathway. Therefore, our experiments suggest the possible future use of miR-16 as a therapeutic target in gliomas.

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