miR-6858 plays a key role in the process of melatonin inhibition of the malignant biological behavior of glioma |
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| Institution: | 1. Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China;2. Shandong Key Laboratory of Brain Function Remodeling, PR China;3. Department of Biomedicine, University of Bergen, 5009 Bergen, Norway;1. Department of Biomedical Engineering, Wroclaw University of Science and Technology, Wroclaw, Poland;2. Department of Neurosurgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS FT, Birmingham, United Kingdom;3. Department of Anaesthesiology and Intensive Care, Wroclaw Medical University, Wroclaw, Poland;4. Department of Neurosurgery, Wroclaw Medical University, Wroclaw, Poland;1. Department of Head & Neck Surgery, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States;2. Department of Neurosurgery, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States;3. Department of Radiation Oncology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States;4. Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States;5. Department of Neurosurgery, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States;6. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States;1. Department of Neurological Surgery, University of Washington, 325 Ninth Ave, Box 359924, Seattle, WA 98104, USA;2. University of Minnesota, 3 Morrill Hall, 100 Church St. S.E, Minneapolis, MN 55455, USA;3. Department of Neurosurgery, Loma Linda University Health, 11234 Anderson St., Suite 2562B, Loma Linda, CA 92354, USA;4. Department of Neurosurgery, University of Texas Health San Antonio, 7703 Floyd Curl Drive, MC 7843, San Antonio, TX 78229, USA;1. Department of Surgery, University of Melbourne, Centre for Medical Research, 300 Grattan Street, Parkville, VIC 3050, Australia;2. Department of Neurosurgery, Royal Melbourne Hospital, 300 Grattan Street, Parkville, VIC 3050, Australia;1. Hospital Madre Teresa, Belo Horizonte, MG, Brazil;2. Hospital Municipal Miguel Couto, Rio de Janeiro, RJ, Brazil;3. University of Vanderbilt, School of Medicine, Nashville, TN, USA;4. Universidade Federal Fluminense, Rio de Janeiro, RJ, Brazil |
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| 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. |
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| Keywords: | Melatonin mir-6858 Proliferation Invasion Glioma |
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