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miR-6858 plays a key role in the process of melatonin inhibition of the malignant biological behavior of glioma

  • Author Footnotes
    1 Contributed equally
    Chenglong Wang
    Footnotes
    1 Contributed equally
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
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  • Author Footnotes
    1 Contributed equally
    Zhimin Zhao
    Footnotes
    1 Contributed equally
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
    Search for articles by this author
  • Qichao Qi
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
    Search for articles by this author
  • Jiwei Wang
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
    Search for articles by this author
  • Yang Kong
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
    Search for articles by this author
  • Zichao Feng
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
    Search for articles by this author
  • Anjing Chen
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
    Search for articles by this author
  • Wenjie Li
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
    Search for articles by this author
  • Qing Zhang
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
    Search for articles by this author
  • Jian Wang
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China

    Department of Biomedicine, University of Bergen, 5009 Bergen, Norway
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  • Bin Huang
    Correspondence
    Corresponding authors at: Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Brain Function Remodeling, 107 Wenhua Xi Road, Jinan 250012, PR China.
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
    Search for articles by this author
  • Xingang Li
    Correspondence
    Corresponding authors at: Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Brain Function Remodeling, 107 Wenhua Xi Road, Jinan 250012, PR China.
    Affiliations
    Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China

    Shandong Key Laboratory of Brain Function Remodeling, PR China
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally

      Highlights

      • Melatonin elevates miR-6858-5p level of GBM cells.
      • Melatonin inhibit GBM progression through miR-6858-5p/SIRT3/AKT signaling pathway.
      • Melatonin inhibits growth of GBM cells in vivo.

      Abstract

      MicroRNAs (miRNAs), small non-coding RNA molecules with a length of 18–25 nucleotides, have been shown to be involved in mediating various malignant properties of GBM, including growth, invasion and angiogenesis. Here, we investigated whether miRNAs might be involved in mediating the suppression of malignant properties of GBM by melatonin (MEL), an amine hormone secreted by the pineal gland. Sequencing was performed to screen specifically for miRNAs induced by MEL in U87 and an orthotopically xenografted primary GBM cell line, GBM#P3. MiR-6858-5p was the most significantly up-regulated miR in GBM cell lines in response to MEL (~5 × ). Transfection of a mimic of miR-6858-5p into both cell lines led to a decrease in viability of ~ 50% at 72 h, confirming a suppressive role for miR-6858-5p in GBM. In contrast, an inhibitor of miR-6858-5p rescued GBM cells from MEL suppression of proliferation, migration and invasion. Analysis using Targetscan yielded candidate mRNAs targeted by miR-6858-5p, some of which are involved in the SIRT/AKT signaling pathway. In cells transfected with a mimic or an inhibitor of miR-6858-5p, levels of SIRT3 and downstream components of the AKT signaling pathway were suppressed or up-regulated, respectively, both in vitro and in an in vivo orthotopic xenograft model. Our results elucidated a novel molecular mechanism underlying MEL suppression of GBM, highlighting a role for miRNAs, and provide a potential therapeutic strategy for GBM.

      Keywords

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