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

Journal of Translational Medicine

Chunsheng Kang⁵  Peiyu Pu⁷  Meili Liu¹  Jinhuan Wang⁶  Tao Jiang³  Yongping You²  Shizhu Yu⁷  Lei Han⁴  Yingyi Wang²  Zhendong Shi⁷  Jianwei Hao⁷  Junxia Zhang²  Chunzhi Zhang⁷ 

[1] Department of Radiology, Tianjin Huanhu Hospital, Tianjin, 300060, China;Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China;Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, 100050, China;Department of Neurosurgery, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China;Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, 300052, China;Department of Radiation Oncology, Tianjin Huanhu hospital, Tianjin, 300060, 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, Tianjin, 300052, China

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

Others  :  1205962
DOI  :  10.1186/1479-5876-10-119

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

【 摘 要 】

Background

MiR-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.

Methods

Invasion 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.

Results

MiR-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.

Conclusions

The 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】

   
2012 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

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