High level of miR-221/222 confers increased cell invasion and poor prognosis in glioma

Journal of Translational Medicine

Research

Lei Han¹  Jianwei Hao²  Peiyu Pu²  Zhendong Shi²  Junxia Zhang³  Chunsheng Kang⁴  Yongping You⁵  Yingyi Wang⁵  Tao Jiang⁶  Jinhuan Wang⁷  Chunzhi Zhang⁸  Meili Liu⁹  Shizhu Yu^1,10 

[1] Department of Neurosurgery, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, 300052, Tianjin, China;Department of Neurosurgery, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, 300052, Tianjin, China;Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 300052, Tianjin, China;Department of Neurosurgery, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, 300052, Tianjin, China;Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 300052, Tianjin, China;Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China;Department of Neurosurgery, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, 300052, Tianjin, China;Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 300052, Tianjin, China;Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, 300052, Tianjin, China;Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China;Department of Neurosurgery, Tiantan Hospital, Capital Medical University, 100050, Beijing, China;Department of Radiation Oncology, Tianjin Huanhu hospital, 300060, Tianjin, China;Department of Radiation Oncology, Tianjin Huanhu hospital, 300060, Tianjin, China;Department of Neurosurgery, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, 300052, Tianjin, China;Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 300052, Tianjin, China;Department of Radiology, Tianjin Huanhu Hospital, 300060, Tianjin, China;Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 300052, Tianjin, China;

关键词: MiRNA;    TIMP3;    Glioblastoma;    Cell invasion;    Prognosis;   

DOI  :  10.1186/1479-5876-10-119

 received in 2011-11-23, accepted in 2012-06-08,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMiR-221 and miR-222 (miR-221/222), upregulated in gliomas, can regulate glioma cell cycle progression and apoptosis, respectively. However, the association of miR-221/222 with glioma cell invasion and survival remains unknown.MethodsInvasion capability of miR-221/222 was detected by mutiple analyses, including diffusion tensor imaging (DTI), transwell, wound healing and nude mouse tumor xenograft model assay. Further, the target of miR-221/222 was determined by luciferase reporter, western blot and gene rescue assay. The association of miR-221/222 with outcome was examined in fifty glioma patients.ResultsMiR-221/222 expression was significantly increased in high-grade gliomas compared with low-grade gliomas, and positively correlated with the degree of glioma infiltration. Over-expression of miR-221/222 increased cell invasion, whereas knockdown of miR-221/222 decreased cell invasion via modulating the levels of the target, TIMP3. Introduction of a TIMP3 cDNA lacking 3’ UTR abrogated miR-221/222-induced cell invasion. In addition, knockdown of miR-221/222 increased TIMP3 expression and considerably inhibited tumor growth in a xenograft model. Finally, the increased level of miR-221/222 expression in high-grade gliomas confers poorer overall survival.ConclusionsThe present data indicate that miR-221 and miR-222 directly regulate cell invasion by targeting TIMP3 and act as prognostic factors for glioma patients.

【 授权许可】

Unknown   
© Zhang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.