miR-361-5p inhibits glioma migration and invasion by targeting SND1
Received 18 April 2018
Accepted for publication 1 June 2018
Published 28 August 2018 Volume 2018:11 Pages 5239—5252
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Takuya Aoki
Jing Liu,1,2,* Jie Yang,3,* Lin Yu,3,* Chun Rao,2,4,5 Qian Wang,2,4,5 Cuiyun Sun,2,4,5 Cuijuan Shi,2,4,5 Dan Hua,2,4,5 Xuexia Zhou,2,4,5 Wenjun Luo,2,4,5 Run Wang,2,4,5 Weiping Li,1 Shizhu Yu2,4,5
1Department of Neurosurgery and Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen University School of Medicine, Shenzhen 518035, People’s Republic of China; 2Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Tianjin Medical University,Tianjin 300070, People’s Republic of China; 4Department of Neuropathology, Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, People’s Republic of China; 5Department of Neuropathology, Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, People’s Republic of China
*These authors contributed equally to this work
Background: Downregulation of miR-361-5p contributes to epithelial–mesenchymal transition of glioma cells. However, the relevance of miR-361-5p to migration and invasion of gliomas remains unknown.
Materials and methods: The relationship between miR-361-5p and SND1 expression was analyzed in 120 human gliomas and 8 glioma cell lines by in situ hybridization, immunohistochemistry, and Western blot. Dual-luciferase reporter assay was used to identify SND1 as a target of miR-361-5p. The mechanisms through which miR-361-5p inhibits glioma cell migration and invasion were studied by in vitro assays.
Results: miR-361-5p expression was significantly downregulated in glioma tissues and glioma cell lines, and was inversely correlated with glioma grades. However, SND1 expression was positively correlated with glioma grades and inversely correlated with miR-361-5p expression. miR-361-5p overexpression suppressed glioma cell migration and invasion through targeting SND1 and subsequently decreasing MMP-2 expression. In glioma cell lines, SND1 overexpression could partly reverse the antitumor effects of miR-361-5p.
Conclusion: The findings provide evidence that miR-361-5p directly targets SND1 to degradation and then reduces MMP-2 gene transcription, thus inhibiting glioma migration and invasion. miR-361-5p is an important tumor suppressor and a novel diagnostic biomarker of glioma, and miR-361-5p and SND1 are potential therapeutic candidates for malignant gliomas.
Keywords: miR-361-5p, glioma, SND1, migration, invasion
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