Silencing of microRNA-708 promotes cell growth and epithelial-to-mesenchymal transition by activating the SPHK2/AKT/β-catenin pathway in glioma
| Autor: | Kewan Wang, Pengwei Shi, Dong Xiao, Mei Lian, Xu-Bin Deng, Hao Long, Hongxiao Wang, Dadi Qian, Weiquan Chen, Yan Chen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Epithelial-Mesenchymal Transition Transplantation Heterologous Immunology Down-Regulation Mice Nude Methylation Article Histones Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Cell Line Tumor Glioma microRNA medicine Animals Humans lcsh:QH573-671 Phosphorylation Protein kinase B beta Catenin Cell Proliferation Cancer Oncogene lcsh:Cytology Brain Neoplasms Cell growth Chemistry Cell Cycle EZH2 Glycogen Synthase Kinases Cell Biology Prognosis medicine.disease Gene Expression Regulation Neoplastic MicroRNAs Phosphotransferases (Alcohol Group Acceptor) SPHK2 030104 developmental biology 030220 oncology & carcinogenesis Catenin Cancer research Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 10, Iss 6, Pp 1-13 (2019) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-019-1671-5 |
| Popis: | Aberrant microRNA-708 (miR-708) expression is frequently reported in cancer studies; however, its role in glioma has not been examined in detail. We investigated miR-708 function in glioma and revealed that miR-708 expression was significantly down-regulated in glioma tissues and cell lines. Restoration of miR-708 inhibited glioma cell growth and invasion both in vitro and in vivo. The oncogene SPHK2 (sphingosine kinase 2) was identified as a downstream target of miR-708 using luciferase and western blot assays. miR-708 inhibited AKT/β-catenin signaling, which is activated by SPHK2. In addition, we revealed that miR-708 was transcriptionally repressed by EZH2 (enhancer of zeste homolog 2)-induced histone H3 lysine 27 trimethylation and promoter methylation. In summary, our findings revealed that miR-708 is a glioma tumor suppressor and suggest that miR-708 is a potential therapeutic target for glioma patients. |
| Databáze: | OpenAIRE |
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