PT  - JOURNAL ARTICLE
AU  - Liu, Liping
AU  - Chen, Kun
AU  - Wu, Jueheng
AU  - Shi, Ling
AU  - Hu, Bo
AU  - Cheng, Shiyuan
AU  - Li, Mengfeng
AU  - Song, Libing
TI  - Downregulation of miR-452 Promotes Stem-Like Traits and Tumorigenicity of Gliomas
AID  - 10.1158/1078-0432.CCR-12-3794
DP  - 2013 Jul 01
TA  - Clinical Cancer Research
PG  - 3429--3438
VI  - 19
IP  - 13
4099  - http://clincancerres.aacrjournals.org/content/19/13/3429.short
4100  - http://clincancerres.aacrjournals.org/content/19/13/3429.full
SO  - Clin Cancer Res2013 Jul 01; 19
AB  - Purpose: miR-452 is reported to be required for neural crest stem cell differentiation during neural crest development. However, the biologic role of miR-452 in gliomas remains unclear. The aim of the present study was to evaluate the effect of miR-452 on the stem-like properties and tumorigenesis of glioma cells. Experimental Design: The expression of miR-452 was examined in glioma cells and glioma tissues using real-time PCR. The effects of miR-452 on stem-like traits and tumorigenesis were investigated in vitro and in vivo using patient-derived glioma cells and glioma cell lines. Western blotting and luciferase reporter assays were conducted to examine the negative regulation of Bmi-1, LEF1, and TCF4 by miR-452. The methylation of the miR-452 promoter region was examined by bisulfite genomic sequencing PCR. Results: miR-452 was markedly downregulated in glioma cells and clinical glioma tissues. miR-452 levels were inversely correlated with World Health Organization (WHO) grades and patient survival. miR-452 directly targeted and suppressed multiple stemness regulators, including Bmi-1, LEF1, and TCF4, resulting in reduced stem-like traits and tumorigenesis of glioma cells in vitro and in vivo. Furthermore, we showed that downregulation of miR-452 in gliomas was caused by hypermethylation of its promoter region. Conclusions: Downregulation of miR-452 plays an important role in promoting the stem-like traits and tumorigenesis of gliomas and may represent a novel prognostic biomarker and therapeutic target for the disease. Clin Cancer Res; 19(13); 3429–38. ©2013 AACR.