机构：[1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China,研究所北京市神经外科研究所首都医科大学附属天坛医院[2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China,重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[3]Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilong Jiang Province 150086, China,[4]Hematological Department, Harbin Institute of Hematology and Oncology, Harbin, Heilong Jiang Province 150010, China,
Gliomas are characterized by a malignant phenotype with proliferation, cell cycle arrest and invasion. To explore the biological consequences of epigenetically regulated miRNAs, we performed a microarray-based screening (whose expression was affected by 5-AZA treatment) followed by bisulfite sequencing validation. We found that miR-134 as an epigenetically regulated suppressor gene with prognostic value in gliomas. MicroRNA-134 was downregulated in high-grade gliomas, especially in GBM samples. Functional studies in vitro and in vivo in mouse models showed that overexpression of miR-134 was sufficient to reduce cell cycle arrest, cell proliferation and invasion. Target analysis and functional assays correlated the malignant phenotype with miR-134 target gene KRAS, an established upstream regulator of ERK and AKT pathways. Overall, our results highlighted a role for miR-134 in explaining the malignant phenotype of gliomas and suggested its relevance as a target to develop for early diagnostics and therapy.
基金：
National Nature Science Foundation of ChinaNational Natural Science Foundation of China [81502494, 81402052, 81502495, 81702460, 81502606]; Natural Science Foundation of Heilongjiang ProvinceNatural Science Foundation of Heilongjiang Province [H2016026]; China Postdoctoral Science Foundation Special Funding [2017T100252, 2016M590293]; Postdoctoral Fund of Heilongjiang Province [LRB14-422]; National Key Research and Development Plan [2016YFC0902500]; Capital Medical Development Research Fund [2016-1-1072]
第一作者机构：[1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China,
共同第一作者：
通讯作者：
通讯机构：[3]Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilong Jiang Province 150086, China,
推荐引用方式(GB/T 7714)：
Zhi-liang Wang,Chuan-bao Zhang,Zheng Wang,et al.MiR-134, epigenetically silenced in gliomas, could mitigate the malignant phenotype by targeting KRAS[J].CARCINOGENESIS.2018,39(3):389-396.doi:10.1093/carcin/bgy022.
APA：
Zhi-liang Wang,Chuan-bao Zhang,Zheng Wang,Xiang-qi Meng,Xiao-juan Liu...&Hong-jun Wang.(2018).MiR-134, epigenetically silenced in gliomas, could mitigate the malignant phenotype by targeting KRAS.CARCINOGENESIS,39,(3)
MLA：
Zhi-liang Wang,et al."MiR-134, epigenetically silenced in gliomas, could mitigate the malignant phenotype by targeting KRAS".CARCINOGENESIS 39..3(2018):389-396
